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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 worldwide.However,due to its complexity,it ranks 7th in the list of the most lethal cancers worldwide.The pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and smoking.Mutations in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,cancer.In 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 efficiency.It 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 cells.Linked 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 interferon-gamma.In this way,finding new strategies that make it possible to manipulate resistance mechanisms is necessary.Thus,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 therapy.Thus,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process,resulting in a more efficient therapy

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

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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 cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This 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 ramifications.Examining 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 lymphoma.Gastric mucosa-associated lymphoid tissue lymphoma(GML)is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori(H.pylori)-induced chronic gastritis.On the other hand,a specific subset of individuals diagnosed with GML does not exhibit H.pylori infection.In contrast to its H.pylori-positive counterpart,it was previously believed that H.pylori-negative GML was less likely to respond to antimicrobial therapy.Despite this,surprisingly,increasing evidence supports that a considerable proportion of patients with H.pylori-negative GML show complete histopathological remission after bacterial eradication therapy.Nonetheless,the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended.In recent years,there has been growing interest in investigating the role of non-H.pylori gastric helicobacters(NHPHs)in the pathogenesis of H.pylori-negative GML.However,additional research is required to establish the causal relationship between NHPHs and GML.In this minireview,we examined the current understanding and proposed prospects on the involvement of NHPHs in H.pylori-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(H.pylori)is a Gram-negative bacterium that infects about half of the world's population.H.pylori 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 H.pylori infection.In this sense,small regulatory RNAs(sRNAs)are important macromolecules capable of inhibiting and activating gene expression.This function allows sRNAs to act in adjusting to unstable environmental conditions and in responding to cellular stresses in bacterial infections.Recent discoveries have shown that nickelregulated small RNA(NikS)is a post-transcriptional regulator of virulence properties of H.pylori,including the oncoprotein CagA.Notably,high concentrations of nickel cause the reduction of NikS expression and consequently this increases the levels of CagA.In addition,NikS expression appears to be lower in clinical isolates from patients with gastric cancer when compared to patients without.With 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 H.pylori 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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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(H.pylori)-induced chronic gastritis.Clinical practice guidelines currently recommend H.pylori eradication as the preferred initial treatment for early-stage GML.To 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 imperative.AIM To perform a meta-analysis to assess the rate of complete remission(CR)of H.pylori-positive early-stage GML following bacterial eradication.METHODS We performed independent,computer-assisted literature searches using the PubMed/MEDLINE,Embase,and Cochrane Central databases through September 2022.Prospective and retrospective observational studies evaluating the CR of early-stage GML following bacterial eradication in H.pylori-positive patients.The risk of bias was assessed using Joanna Briggs Institute(JBI)Critical Appraisal Tools.The pooled estimate of the complete histopathological remission rate and respective confidence intervals(95%CI)were calculated following the random-effects model.Heterogeneity and inconsistency were assessed using Cochran’s Q test and I2 statistic,and heterogeneity was defined as P50%,respectively.Subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity.RESULTS The titles and abstracts of 1576 studies were screened;96 articles were retrieved and selected for full-text reading.Finally,61 studies were included in the proportional meta-analysis(P-MA).Forty-six were prospective and fifteen were retrospective uncontrolled,single-arm,observational studies.The 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 H.pylori-positive early-stage GML patients,in whom H.pylori was successfully eradicated,were included in the analysis.The pooled CR of H.pylori-p

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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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 years.While adults suffered the highest morbidity and mortality rates of coronavirus disease 2019,children were thought to be exclusively asymptomatic or to present with mild conditions.However,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 involvement.The 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 infection.Despite its severity,there are no definitive disease management guidelines for this condition.Conversely,the complex pathogenesis of MIS-C is still not completely understood,although it seems to rely upon immune dysregu-lation.Hence,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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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 negative.However,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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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 worldwide.Helicobacter 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 neoplasms.CagA is the most important virulence factor in H.pylori,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 lesions.Upon 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 apoptosis.All these alterations in cell biology increase the risk of damaged cells acquiring pro-oncogenic genetic changes.In this sense,once gastric cancer sets in,its perpetuation is independent of the presence of the oncoprotein,characterizing a“hit-and-run”carcinogenic mechanism.Therefore,this review aims to describe H.pylori-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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Immunotherapy in glioblastoma treatment:Current state and future prospects

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World Journal of Clinical Oncology 2023年第4期14卷 138-159页

作者： samuel luca rocha pinheiro Fabian Fellipe Bueno Lemos Hanna Santos Marques Marcel Silva Luz Luís Guilherme de Oliveira Silva Clara Faria Souza Mendes dos Santos Karolaine da Costa Evangelista Mariana Santos Calmon Matheus Sande Loureiro 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

Glioblastoma remains as the most common and aggressive malignant brain tumor,standing with a poor prognosis and treatment prospective.Despite the aggressive standard care,such as surgical resection and chemoradiation,median survival rates are low.In this regard,immunotherapeutic strategies aim to become more attractive for glioblastoma,considering its recent advances and approaches.In this review,we provide an overview of the current status and progress in immunotherapy for glioblastoma,going through the fundamental knowledge on immune targeting to promising strategies,such as Chimeric antigen receptor T-Cell therapy,immune checkpoint inhibitors,cytokine-based treatment,oncolytic virus and vaccine-based techniques.At last,it is discussed innovative methods to overcome diverse challenges,and future perspectives in this area.

关键词： Glioblastoma Immunotherapy Tumor microenvironment Chimeric antigen receptor T cell Oncolytic viruses Immune-checkpoint inhibitors Brain cancer

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COVID-19 neuropsychiatric repercussions:Current evidence on the subject

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World Journal of Methodology 2022年第5期12卷 365-380页

作者： Ronaldo Teixeira da Silva Júnior Jonathan Santos Apolonio Beatriz rocha Cuzzuol Bruna Teixeira da Costa Camilo Santana Silva Glauber rocha Lima Araújo Marcel Silva Luz Hanna Santos Marques Luana Kauany de SáSantos samuel luca rocha pinheiro Vinícius Lima de Souza Gonçalves Mariana Santos Calmon Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029094Brazil Universidade Estadual do Sudoeste da Bahia Universidade Estadual do Sudoeste da BahiaVitória da Conquista 45083900Brazil

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has affected the entire world,causing the coronavirus disease 2019(COVID-19)pandemic since it was first discovered in Wuhan,China in December 2019.Among the clinical presentation of the disease,in addition to fever,fatigue,cough,dyspnea,diarrhea,nausea,vomiting,and abdominal pain,infected patients may also experience neurological and psychiatric repercussions during the course of the disease and as a post-COVID-19 sequelae.Thus,headache,dizziness,olfactory and gustatory dysfunction,cerebrovascular disorders,neuromuscular abnormalities,anxiety,depression,and post-traumatic stress disorder can occur both from the infection itself and from social distancing and quarantine.According to current evidence about this infection,the virus has the ability to infect the central nervous system(CNS)via angiotensin-converting enzyme 2(ACE2)receptors on host cells.Several studies have shown the presence of ACE2 in nerve cells and nasal mucosa,as well as transmembrane serine protease 2,key points for interaction with the viral Spike glycoprotein and entry into the CNS,being olfactory tract and blood-brain barrier,through hematogenous dissemination,potential pathways.Thus,the presence of SARS-CoV-2 in the CNS supports the development of neuropsychiatric symptoms.The management of these manifestations seems more complex,given that the dense parenchyma and impermeability of brain tissue,despite protecting the brain from the infectious process,may hinder virus elimination.Still,some alternatives used in non-COVID-19 situations may lead to worse prognosis of acute respiratory syndrome,requiring caution.Therefore,the aim of this review is to bring more current points related to this infection in the CNS,as well as the repercussions of the isolation involved by the pandemic and to present perspectives on interventions in this scenario.

关键词： SARS-CoV-2 COVID-19 Central nervous system Quarantine Neurologic disorders Mental disorders

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