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New avenues for the treatment of immunotherapy-resistant pancreatic cancer

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： Luis Guilherme de Oliveira Silva fabian fellipe bueno lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Mariana dos Santos Calmon Gabriel Lima Correa Santos Gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases ***,due to its complexity,it ranks 7th in the list of the most lethal cancers *** pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and *** in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,*** this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy *** is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive *** to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as *** this way,finding new strategies that make it possible to manipulate resistance mechanisms is ***,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC ***,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating thi

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation Combined immunotherapy

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Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy

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World Journal of Gastroenterology 2024年第6期30卷 579-598页

作者： fabian fellipe bueno lemos Caroline Tianeze de Castro Marcel Silva Luz Gabriel Reis Rocha Gabriel Lima Correa Santos Luís Guilherme de Oliveira Silva Mariana Santos Calmon Cláudio Lima Souza Ana Carla Zarpelon-Schutz Kádima Nayara Teixeira Dulciene Maria de Magalhães Queiroz Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Instituto de Saúde Coletiva Universidade Federal da BahiaSalvador 40110040BahiaBrazil Campus Toledo Universidade Federal do ParanáToledo 85919-899ParanáBrazil Laboratory of Research in Bacteriology UFMGBelo Horizonte 30130-100Minas GeraisBrazil

BACKGROUND Helicobacter pylori(***)infection has been well-established as a significant risk factor for several gastrointestinal *** urea breath test(UBT)has emerged as a leading non-invasive method for detecting *** numerous studies confirming its substantial accuracy,the reliability of UBT results is often compromised by inherent *** findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of *** *** To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for *** infection in adult patients with *** We conducted an independent search of the PubMed/MEDLINE,EMBASE,and Cochrane Central databases until April *** search included diagnostic accuracy studies that evaluated at least one of the index tests(^(13)C-UBT or ^(14)C-UBT)against a reference *** used the QUADAS-2 tool to assess the methodo-logical quality of the *** utilized the bivariate random-effects model to calculate sensitivity,specificity,positive and negative test likelihood ratios(LR+and LR-),as well as the diagnostic odds ratio(DOR),and their 95%confidence *** conducted subgroup analyses based on urea dosing,time after urea administration,and assessment *** investigate a possible threshold effect,we conducted Spearman correlation analysis,and we generated summary receiver operating characteristic(SROC)curves to assess ***,we visually inspected a funnel plot and used Egger’s test to evaluate publication *** both as reliable diagnostic tools in clinical *** In summary,our study has demonstrated that ^(13)C-UBT has been found to outperform the ^(14)C-UBT,making it the preferred diagnostic ***,our results emphasize the significance of carefully considering urea dosage,assessment timing,and measurement techniques for both tests to enh

关键词： Helicobacter pylori Urea breath test Diagnosis Diagnostic test accuracy Meta-analysis

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Immune pathway through endometriosis to ovarian cancer

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World Journal of Clinical Oncology 2024年第4期15卷 496-522页

作者： Mariana Santos Calmon fabian fellipe bueno lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Luis Guilherme de Oliveira Silva Gabriel Lima Correa Santos Gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine *** disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic *** endometriosis is a benign disease,it shares several characteristics with invasive *** support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic *** is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and ***,the carcinogenic pathways between both pathologies remain poorly *** studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and *** article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their *** recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

关键词： Ovarian neoplasms Endometriosis Endometriosis-associated ovarian cancers Immune response Immunotherapy

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Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma

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世界胃肠病学杂志:英文版 2023年第32期29卷 4851-4859页

作者： fabian fellipe bueno lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Kádima Nayara Teixeira Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029094Brazil Campus Toledo Universidade Federal do ParanáToledo 85919899Brazil

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma,trailing behind diffuse large B-cell lymphoma and follicular *** mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(***)-induced chronic *** the other hand,a specific subset of individuals diagnosed with GML does not exhibit *** *** contrast to its ***-positive counterpart,it was previously believed that ***-negative GML was less likely to respond to antimicrobial *** this,surprisingly,increasing evidence supports that a considerable proportion of patients with ***-negative GML show complete histopathological remission after bacterial eradication ***,the precise mechanisms underlying this treatment responsiveness are not yet fully *** recent years,there has been growing interest in investigating the role of *** gastric helicobacters(NHPHs)in the pathogenesis of ***-negative ***,additional research is required to establish the causal relationship between NHPHs and *** this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in ***-negative GML,as well as their potential response to bacterial eradication therapy.

关键词： Lymphoma B cell Marginal zone Gastric mucosa-associated lymphoid tissue lymphoma Helicobacter pylori Non-Helicobacter pylori gastric helicobacters Helicobacter heilmannii Helicobacter suis

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Role of nickel-regulated small RNA in modulation of Helicobacter pylori virulence factors

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World Journal of Clinical Cases 2022年第31期10卷 11283-11291页

作者： Fabrício Freire de Melo Hanna Santos Marques fabian fellipe bueno lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Lorena Sousa de Carvalho Cláudio Lima Souza Márcio Vasconcelos Oliveira Institution Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094Brazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45083-900Brazil

Helicobacter pylori(***)is a Gram-negative bacterium that infects about half of the world's *** infection prevails by several mechanisms of adaptation of the bacteria and by its virulence factors including the cytotoxin associated antigen A(CagA).CagA is an oncoprotein that is the protagonist of gastric carcinogenesis associated with prolonged *** *** this sense,small regulatory RNAs(sRNAs)are important macromolecules capable of inhibiting and activating gene *** function allows sRNAs to act in adjusting to unstable environmental conditions and in responding to cellular stresses in bacterial *** discoveries have shown that nickelregulated small RNA(NikS)is a post-transcriptional regulator of virulence properties of ***,including the oncoprotein ***,high concentrations of nickel cause the reduction of NikS expression and consequently this increases the levels of *** addition,NikS expression appears to be lower in clinical isolates from patients with gastric cancer when compared to patients *** that in mind,this minireview approaches,in an accessible way,the most important and current aspects about the role of NikS in the control of virulence factors of *** and the potential clinical repercussions of this modulation.

关键词： Helicobacter pylori Small regulatory RNAs Nickel-regulated small RNA Virulence factors Cytotoxin associated antigen A Gastric cancer

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Usher syndrome:Genetic diagnosis and current therapeutic approaches

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World Journal of Otorhinolaryngology 2024年第1期11卷 1-17页

作者： Beatriz Rocha Cuzzuol Jonathan Santos Apolonio Ronaldo Teixeira da Silva Júnior Lorena Sousa de Carvalho Luana Kauany de SáSantos Luciano Hasimoto Malheiro Marcel Silva Luz Mariana Santos Calmon Henrique de Lima Crivellaro fabian fellipe bueno lemos Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Usher Syndrome(USH)is the most common deaf-blind syndrome,affecting approximately 1 in 6000 people in the deaf *** genetic condition is characterized by a combination of hearing loss(HL),retinitis pigmentosa,and,in some cases,vestibular *** the subtypes of USH,USH type 1 is considered the most severe form,presenting profound bilateral congenital deafness,vestibular areflexia,and early onset *** type 2 is the most common form,exhibiting congenital moderate to severe HL for low frequencies and severe to profound HL for high ***,type 3 is the rarest,initially manifesting mild symptoms during childhood that become more prominent in the first decades of *** dual impact of USH on both visual and auditory senses significantly impairs patients'quality of life,restricting their daily activities and interactions with *** date,9 genes have been confirmed so far for USH:MYO7A,USH1C,CDH23,PCDH15,USH1G,USH2A,ADGRV1,WHRN and *** genes are inherited in an autosomal recessive manner and encode proteins expressed in the inner ear and retina,leading to functional *** non-genetic methods can assist in patient triage and disease extension evaluation,genetic and molecular tests play a pivotal role in providing genetic counseling,enabling appropriate gene therapy,and facilitating timely cochlear implantation(CI).The CRISPR/Cas9 system and viral-based gene replacement therapy have recently emerged as highly promising techniques for treating *** drug therapy,PTC-124 and Nb54 have been identified as promising drug interventions for genetic HL in ***,CI has proven to be critical in the restoration of *** review aims to summarize the genetic and molecular diagnosis of USH and highlight the importance of early diagnosis in Cuzzuol BR et *** and current treatments of USH WJO https://*** 2 January 19,2024 Volume 11 Issue 1 guiding appropriate treatment strategies and i

关键词： Usher syndromes Hearing loss Retinitis pigmentosa Diagnosis Genetic therapies Cochlear implantation Quality of life

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Effectiveness of Helicobacter pylori eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma:An up-to-date meta-analysis

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World Journal of Gastroenterology 2023年第14期29卷 2202-2221页

作者： fabian fellipe bueno lemos Caroline Tianeze de Castro Mariana Santos Calmon Marcel Silva Luz Samuel Luca Rocha Pinheiro Clara Faria Souza Mendes dos Santos Gabriel Lima Correa Santos Hanna Santos Marques Henrique Affonso Delgado Kádima Nayara Teixeira Cláudio Lima Souza Márcio Vasconcelos Oliveira Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029094BahiaBrazil Instituto de Saúde Coletiva Universidade Federal da BahiaSalvador 40110040BahiaBrazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45029094BahiaBrazil Campus Toledo Universidade Federal do ParanáToledo 85919899ParanáBrazil

BACKGROUND Gastric mucosa-associated lymphoid tissue(MALT)lymphoma(GML)is usually a low-grade B-cell neoplasia strongly associated with Helicobacter pylori(***)-induced chronic *** practice guidelines currently recommend *** eradication as the preferred initial treatment for early-stage *** determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML,an updated analysis and review of available evidence is *** To perform a meta-analysis to assess the rate of complete remission(CR)of ***-positive early-stage GML following bacterial *** We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September *** and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in ***-positive *** risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal *** pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects *** and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P50%,*** and meta-regression analyses were conducted to explore potential sources of *** The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text ***,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational *** overall risk of bias was low to moderate in all but a single report,with an average critical appraisal score across all studies of 79.02%.A total of 2936 ***-positive early-stage GML patients,in whom *** was successfully eradicated,were incl

关键词： Lymphoma B-cell Marginal zone Gastric mucosa-associated lymphoid tissue lymphoma Stomach lymphoma Helicobacter pylori Therapeutics Eradication therapy

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Influence of Helicobacter pylori oncoprotein CagA in gastric cancer:A critical-reflective analysis

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World Journal of Clinical Oncology 2022年第11期13卷 866-879页

作者： Fabrício Freire de Melo Hanna Santos Marques Samuel Luca Rocha Pinheiro fabian fellipe bueno lemos Marcel Silva Luz Kádima Nayara Teixeira Cláudio Lima Souza Márcio Vasconcelos Oliveira Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094Brazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45029-094Brazil Campus Toledo Universidade Federal do ParanáToledo 85919899Brazil

Gastric cancer is the fifth most common malignancy and third leading cancerrelated cause of death *** pylori is a Gram-negative bacterium that inhabits the gastric environment of 60.3%of the world’s population and represents the main risk factor for the onset of gastric *** is the most important virulence factor in ***,and is a translocated oncoprotein that induces morphofunctional modifications in gastric epithelial cells and a chronic inflammatory response that increases the risk of developing precancerous *** translocation and tyrosine phosphorylation,CagA moves to the cell membrane and acts as a pathological scaffold protein that simultaneously interacts with multiple intracellular signaling pathways,thereby disrupting cell proliferation,differentiation and *** these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic *** this sense,once gastric cancer sets in,its perpetuation is independent of the presence of the oncoprotein,characterizing a“hit-and-run”carcinogenic ***,this review aims to describe ***-and CagA-related oncogenic mechanisms,to update readers and discuss the novelties and perspectives in this field.

关键词： Helicobacter pylori Virulence factors CagA Gastric cancer EPIYA motifs Hit-and-run carcinogenesis

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Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis:An experimental study in Brazil

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World Journal of Experimental Medicine 2022年第5期12卷 100-103页

作者： Fabrício Freire de Melo Lilian Martins Oliveira Diniz JoséNélio Januário João Fernando Gonçalves Ferreira Rafael Santos Dantas Miranda Dórea Breno Bittencourt de Brito Hanna Santos Marques fabian fellipe bueno lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Dulciene Maria de Magalhães Queiroz Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Departamento de Pediatria Universidade Federal de Minas GeraisBelo Horizonte 31270-901Brazil Núcleo de Ações e Pesquisa em Apoio Diagnóstico Universidade Federal de Minas GeraisBelo Horizonte 31270-901Brazil Laboratory of Research in Bacteriology Universidade Federal de Minas GeraisBelo Horizonte 31270-901Brazil Laboratory of Bacteriology Faculdade de MedicinaUniversidade Federal de Minas GeraisBelo Horizonte 31270-901Brazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45029-094Brazil

Qualitative antibody tests are an easy,point-of-care diagnostic method that is useful in diagnosing coronavirus disease 2019,especially in situations where reverse transcription-polymerase chain reaction is ***,some factors are able to affect its sensitivity and accuracy,which may contribute to these tests not being used as a first-line diagnostic tool.

关键词： Serological test IgM IgG COVID-19 Diagnosis Antibody

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Pediatric multisystem inflammatory syndrome associated with COVID-19: Insights in pathogenesis and clinical management

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World Journal of Virology 2023年第3期12卷 193-203页

作者： Marcel Silva Luz fabian fellipe bueno lemos Samuel Luca Rocha Pinheiro Hanna Santos Marques Luís Guilherme de Oliveira Silva Mariana Santos Calmon Karolaine da Costa Evangelista Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil Campus Vitória da Conquista Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45029-094BahiaBrazil

The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been a major challenge to be faced in recent *** adults suffered the highest morbidity and mortality rates of coronavirus disease 2019,children were thought to be exclusively asymptomatic or to present with mild ***,around April 2020,there was an outbreak of a new clinical syndrome related to SARS-CoV-2 in children-multisystemic inflam-matory syndrome in children(MIS-C)-which comprises a severe and uncon-trolled hyperinflammatory response with multiorgan *** Centers for Disease Control and Prevention considers a suspected case of MIS-C an individual aged2)organ involvement,no alternative plausible diagnoses,and positive for recent SARS-CoV-2 *** its severity,there are no definitive disease management guidelines for this ***,the complex pathogenesis of MIS-C is still not completely understood,although it seems to rely upon immune ***,in this study,we aim to bring together current evidence regarding the pathogenic mechanisms of MIS-C,clinical picture and management,in order to provide insights for clinical practice and implications for future research directions.

关键词： Pediatric multisystem inflammatory disease COVID-19 related Multisystem inflammatory syndrome in children COVID-19 SARS-CoV-2 Etiology Disease management

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