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  1. Article: TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells.

    Martins-Cardoso, Karina / Maçao, Aquiles / Souza, Juliana L / Silva, Alexander G / König, Sandra / Martins-Gonçalves, Remy / Hottz, Eugenio D / Rondon, Araci M R / Versteeg, Henri H / Bozza, Patrícia T / Almeida, Vitor H / Monteiro, Robson Q

    Cancers

    2023  Volume 16, Issue 1

    Abstract: Neutrophil extracellular traps (NETs) have been implicated in several hallmarks of cancer. Among the protumor effects, NETs promote epithelial-mesenchymal transition (EMT) in different cancer models. EMT has been linked to an enhanced expression of the ... ...

    Abstract Neutrophil extracellular traps (NETs) have been implicated in several hallmarks of cancer. Among the protumor effects, NETs promote epithelial-mesenchymal transition (EMT) in different cancer models. EMT has been linked to an enhanced expression of the clotting-initiating protein, tissue factor (TF), thus favoring the metastatic potential. TF may also exert protumor effects by facilitating the activation of protease-activated receptor 2 (PAR2). Herein, we evaluated whether NETs could induce TF expression in breast cancer cells and further promote procoagulant and intracellular signaling effects via the TF/PAR2 axis. T-47D and MCF7 cell lines were treated with isolated NETs, and samples were obtained for real-time PCR, flow cytometry, Western blotting, and plasma coagulation assays. In silico analyses were performed employing RNA-seq data from breast cancer patients deposited in The Cancer Genome Atlas (TCGA) database. A positive correlation was observed between neutrophil/NETs gene signatures and TF gene expression. Neutrophils/NETs gene signatures and PAR2 gene expression also showed a significant positive correlation in the bioinformatics model. In vitro analysis showed that treatment with NETs upregulated TF gene and protein expression in breast cancer cell lines. The inhibition of ERK/JNK reduced the TF gene expression induced by NETs. Remarkably, the pharmacological or genetic inhibition of the TF/PAR2 signaling axis attenuated the NETs-induced expression of several protumor genes. Also, treatment of NETs with a neutrophil elastase inhibitor reduced the expression of metastasis-related genes. Our results suggest that the TF/PAR2 signaling axis contributes to the pro-cancer effects of NETs in human breast cancer cells.
    Language English
    Publishing date 2023-12-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers16010005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Sepsis in Brazilian emergency departments: a prospective multicenter observational study.

    Machado, Flávia R / Cavalcanti, Alexandre B / Braga, Maria A / Tallo, Fernando S / Bossa, Aline / Souza, Juliana L / Ferreira, Josiane F / Pizzol, Felipe Dal / Monteiro, Mariana B / Angus, Derek C / Lisboa, Thiago / Azevedo, Luciano C P

    Internal and emergency medicine

    2023  Volume 18, Issue 2, Page(s) 409–421

    Abstract: We aimed to assess the prevalence, patient allocation adequacy, and mortality of adults with sepsis in Brazilian emergency departments (ED) in a point-prevalence 3-day investigation of patients with sepsis who presented to the ED and those who remained ... ...

    Abstract We aimed to assess the prevalence, patient allocation adequacy, and mortality of adults with sepsis in Brazilian emergency departments (ED) in a point-prevalence 3-day investigation of patients with sepsis who presented to the ED and those who remained there due to inadequate allocation. Allocation was considered adequate if the patient was transferred to the intensive care unit (ICU), ward, or remained in the ED without ICU admission requests. Prevalence was estimated using the total ED visit number. Prognostic factors were assessed with logistic regression. Of 33,902 ED visits in 74 institutions, 183 were acute admissions (prevalence: 5.4 sepsis per 1000 visits [95% confidence interval (CI): 4.6-6.2)], and 148 were already in the ED; totaling 331 patients. Hospital mortality was 32% (103/322, 95% CI 23.0-51.0). Age (odds ratio (OR) 1.22 [95% CI 1.10-1.37]), Sequential Organ Failure Assessment (SOFA) score (OR 1.41 [95% CI 1.28-1.57]), healthcare-associated infections (OR 2.59 [95% CI 1.24-5.50]) and low-resource institution admission (OR 2.65 [95% CI 1.07-6.90]) were associated with higher mortality. Accredited institutions (OR 0.42 [95% CI 0.21-0.86]) had lower mortality rates. Allocation within 24 h was adequate in only 52.8% of patients (public hospitals: 42.4% (81/190) vs. private institutions: 67.4% (89/132, p < 0.001) with 39.2% (74/189) of public hospital patients remaining in the ED until discharge, of whom 55.4% (41/74) died. Sepsis exerts high burden and mortality in Brazilian EDs with frequent inadequate allocation. Modifiable factors, such as resources and quality of care, are associated with reduced mortality.
    MeSH term(s) Adult ; Humans ; Prospective Studies ; Brazil/epidemiology ; Hospitalization ; Sepsis/complications ; Hospital Mortality ; Intensive Care Units ; Emergency Service, Hospital ; Retrospective Studies
    Language English
    Publishing date 2023-02-02
    Publishing country Italy
    Document type Observational Study ; Multicenter Study ; Journal Article
    ZDB-ID 2454173-4
    ISSN 1970-9366 ; 1828-0447
    ISSN (online) 1970-9366
    ISSN 1828-0447
    DOI 10.1007/s11739-022-03179-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6673: Show issues Location:
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  3. Article: Interplay Between EGFR and the Platelet-Activating Factor/PAF Receptor Signaling Axis Mediates Aggressive Behavior of Cervical Cancer.

    Souza, Juliana L / Martins-Cardoso, Karina / Guimarães, Isabella S / de Melo, Andréia C / Lopes, Angela H / Monteiro, Robson Q / Almeida, Vitor H

    Frontiers in oncology

    2020  Volume 10, Page(s) 557280

    Abstract: Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. EGFR may be activated by a diversity of mechanisms, including transactivation by G-protein coupled ...

    Abstract Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. EGFR may be activated by a diversity of mechanisms, including transactivation by G-protein coupled receptors (GPCRs). Studies have also shown that platelet-activating factor (PAF), a pro-inflammatory phospholipid mediator, plays an important role in the cancer progression either by modulating the cancer cells or the tumor microenvironment. Most of the PAF effects seem to be mediated by the interaction with its receptor (PAFR), a member of the GPCRs family. PAFR- and EGFR-evoked signaling pathways contribute to tumor biology; however, the interplay between them remains uninvestigated in cervical cancer. In this study, we employed The Cancer Genome Atlas (TCGA) and cancer cell lines to evaluate possible cooperation between EGFR, PAFR, and lysophosphatidylcholine acyltransferases (LPCATs), enzymes involved in the PAF biosynthesis, in the context of cervical cancer. It was observed a strong positive correlation between the expression of EGFR × PAFR and EGFR × LPCAT2 in 306 cervical cancer samples. The increased expression of LPCAT2 was significantly correlated with poor overall survival. Activation of EGFR upregulated the expression of PAFR and LPCAT2 in a MAPK-dependent fashion. At the same time, PAF showed the ability to transactivate EGFR leading to ERK/MAPK activation, cyclooxygenase-2 (COX-2) induction, and cell migration. The positive crosstalk between the PAF-PAFR axis and EGFR demonstrates a relevant linkage between inflammatory and growth factor signaling in cervical cancer cells. Finally, combined PAFR and EGFR targeting treatment impaired clonogenic capacity and viability of aggressive cervical cancer cells more strongly than each treatment separately. Collectively, we proposed that EGFR, LPCAT2, and PAFR emerge as novel targets for cervical cancer therapy.
    Language English
    Publishing date 2020-12-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2020.557280
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Aliphatic fatty acids and esters: inhibition of growth and exoenzyme production of Candida, and their cytotoxicity in vitro: anti-Candida effect and cytotoxicity of fatty acids and esters.

    Souza, Juliana L S / da Silva, Adriana F / Carvalho, Pedro H A / Pacheco, Bruna S / Pereira, Cláudio M P / Lund, Rafael G

    Archives of oral biology

    2014  Volume 59, Issue 9, Page(s) 880–886

    Abstract: The secretion of extracellular phospholipases and proteinases of Candida has been described as a relevant virulence factor in human infections. Aliphatic fatty acids have antimicrobial properties, but the mechanism by which they affect the virulence ... ...

    Abstract The secretion of extracellular phospholipases and proteinases of Candida has been described as a relevant virulence factor in human infections. Aliphatic fatty acids have antimicrobial properties, but the mechanism by which they affect the virulence factors of microorganisms, such as Candida, is still unclear, and there are a few reports about their toxicity. The current study investigated the in vitro antifungal activity, exoenzyme production and cytotoxicity of some aliphatic fatty acids and their ester derivatives against the Candida species. The minimum inhibitory concentration and minimum fungicidal concentrations of aliphatic medium-chain fatty acids, methyl and ethyl esters were performed using the CLSI M27-A3 method and the cytotoxicity assay was performed according to ISO 10993-5. The influence of these compounds in the inhibition of the production of hydrolytic enzymes, phospholipases and proteinases by Candida was also investigated. Data analysis was performed using the one-way ANOVA method (p≤0.05). In relation to the MIC against Candida species, the fatty acid with the best result was Lauric acid, although its ester derivatives showed no activity. The inhibition of phospholipase production was more significant than the inhibition of proteinase production by Candida. Tested fatty acids revealed more than 80% cell viability in their MIC concentrations. Additionally, a cell viability of 100% was reported at concentrations of anti-enzymatic effect. Therefore, the potential use of these fatty acids could be the basis for more antimicrobial tests.
    MeSH term(s) Antifungal Agents/pharmacology ; Candida/drug effects ; Candida/enzymology ; Cell Culture Techniques ; Cell Survival ; Esters/pharmacology ; Fatty Acids/pharmacology ; Fluconazole/pharmacology ; Humans ; In Vitro Techniques ; Microbial Sensitivity Tests ; Peptide Hydrolases/metabolism ; Phospholipases/metabolism ; Virulence Factors
    Chemical Substances Antifungal Agents ; Esters ; Fatty Acids ; Virulence Factors ; Fluconazole (8VZV102JFY) ; Phospholipases (EC 3.1.-) ; Peptide Hydrolases (EC 3.4.-)
    Language English
    Publishing date 2014-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80227-x
    ISSN 1879-1506 ; 0003-9969
    ISSN (online) 1879-1506
    ISSN 0003-9969
    DOI 10.1016/j.archoralbio.2014.05.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ul III Zs.151: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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