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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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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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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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Molecular and serology methods in the diagnosis of COVID-19: An overview

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World Journal of Methodology 2022年第3期12卷 83-91页

作者： Marcel Silva Luz Ronaldo Teixeira da Silva Júnior Gabriella Almeida santos de Santana Gabriela santosRodrigues Henrique de Lima Crivellaro mariana santos calmon Clara Faria Souza Mendes dos santos LuisGuilherme de Oliveira Silva Qesya Rodrigues Ferreira Guilherme Rabelo Mota Heloísa Heim Filipe AntônioFrança da Silva Breno Bittencourt de Brito Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45002175BahiaBrazil Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Coronavirus disease-19(COVID-19)has become a pandemic,being a global health concern since December 2019 when the first cases were reported.Severe acute respiratory syndrome coronavirus 2,the COVID-19 causal agent,is aβ-coronavirus that has on its surface the spike protein,which helps in its virulence and pathogenicity towards the host.Thus,effective and applicable diagnostic methods to this disease come as an important tool for the management of the patients.The use of the molecular technique PCR,which allows the detection of the viral RNA through nasopharyngeal swabs,is considered the gold standard test for the diagnosis of COVID-19.Moreover,serological methods,such as enzyme-linked immunosorbent assays and rapid tests,are able to detect severe acute respiratory syndrome coronavirus 2-specific immunoglobulin A,immunoglobulin M,and immunoglobulin G in positive patients,being important alternative techniques for the diagnostic establishment and epidemiological surveillance.On the other hand,reverse transcription loop-mediated isothermal amplification also proved to be a useful diagnostic method for the infection,mainly because it does not require a sophisticated laboratory apparatus and has similar specificity and sensitivity to PCR.Complementarily,imaging exams provide findings of typical pneumonia,such as the ground-glass opacity radiological pattern on chest computed tomography scanning,which along with laboratory tests assist in the diagnosis of COVID-19.

关键词： COVID-19 Pandemic Diagnosis Polymerase chain reaction Molecular biology Serology

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