Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Silva, Ildefonso; Andrade, Luciana Nogueira de Sousa; Jancar, Sônia; Chammas, Roger

doi:10.6061/clinics/2018/e792s

Cited by 17 publications

(29 citation statements)

References 71 publications

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“…Our results indicate an increase in thrombin generation in breast cancer cells treated with Tamoxifen. Notably both cells lines are implicated in the secretion of Platelet Activating Factor (PAF) under thrombin stimulation, which in addition to mediating platelet aggregation, in an autocrine manner also enhances tumour progression 64,65 ; however, T47D cells appeared to induce a more hypercoagulatory environment than MCF7 cells. Tamoxifen-treated T47D cells induced later stages of platelet activation associated with a loss of CD62P IPA and persistence of CD63 IPA reflecting hypercoagulation in both PRP and WB, compared to MCF7 cells.…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo

Pather

Augustine

2020

Sci Rep

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Tamoxifen shows efficacy in reducing breast cancer-related mortality but clinically, is associated with increased risk for thromboembolic events. We aimed to determine whether breast tumour sub-phenotype could predict propensity for thrombosis. We present two ex vivo Models of Tamoxifen-therapy, Model 1 in which treatment recapitulates accumulation within breast tissue, by treating MCF7 and T47D cells directly prior to exposure to blood constituents; and Model 2 in which we recreate circulating Tamoxifen by treating blood constituents prior to exposure to cancer cells. Blood constituents included whole blood, platelet-rich plasma and platelet-poor plasma. Hypercoagulation was assessed as a function of thrombin activity, expression of CD62P and CD63 activation markers defined as an index of platelet activation, and platelet morphology; while oestrogen receptor expression was assessed using immunocytochemistry with quantitative analysis. We determined, in concert with clinical studies and contrary to selected laboratory investigations, that Tamoxifen induces hypercoagulation, dependent on sub-phenotypes, with the T47D cell line capacity most enhanced. We determined a weak positive correlation between oestrogen receptor expression, and CD62P and CD63; indicating an association between tumour invasion profiles and hypercoagulation, however, other yet unknown factors may play a predictive role in defining hypercoagulation.

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Section: Discussionmentioning

confidence: 99%

Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo

Pather

Augustine

2020

Sci Rep

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“…The LOC100300716 gene is the immunoglobulin heavy variable 4-38-2 that is involved in antigen recognition and is conserved in human and other primates. The PTAFR receptor binds platelet activating factor (PAF), which has been implicated in a number of diseases and disorders like asthma, allergies and is also a lipid mediator of inflammatory responses [46]. These genes underscore the potential involvement that immune responses and inflammatory pathways seem to have with feed efficiency in the mesenteric adipose tissue.…”

Section: Genes Identified For the Gain X Intake Interactionmentioning

confidence: 99%

Genes associated with body weight gain and feed intake identified by meta-analysis of the mesenteric fat from crossbred beef steers

et al. 2020

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Mesenteric fat is a visceral fat depot that increases with cattle maturity and can be influenced by diet. There may be a relationship between the accumulation of mesenteric fat and feed efficiency in beef cattle. The purpose of this study was to identify genes that may be differentially expressed in steers with high and low BW gain and feed intake. RNA-Seq was used to evaluate the transcript abundance of genes in the mesenteric fat from a total of 78 steers collected over 5 different cohorts. A meta-analysis was used to identify genes involved with gain, feed intake or the interaction of both phenotypes. The interaction analysis identified 11 genes as differentially expressed. For the main effect of gain, a total of 87 differentially expressed genes (DEG) were identified (P ADJ <0.05), and 24 were identified in the analysis for feed intake. Genes identified for gain were involved in functions and pathways including lipid metabolism, stress response/protein folding, cell proliferation/growth, axon guidance and inflammation. The genes for feed intake did not cluster into pathways, but some of the DEG for intake had functions related to inflammation, immunity, and/or signal transduction (JCHAIN, RIPK1, LY86, SPP1, LYZ, CD5, CD53, SRPX, and NF2). At P ADJ <0.1, only 4 genes (OLFML3, LOC100300716, MRPL15, and PUS10) were identified as differentially expressed in two or more cohorts, highlighting the importance of evaluating the transcriptome of more than one group of animals and incorporating a meta-analysis. This meta-analysis has produced many mesenteric fat DEG that may be contributing to gain and feed intake in cattle. OPEN ACCESSCitation: Lindholm-Perry AK, Freetly HC, Oliver WT, Rempel LA, Keel BN (2020) Genes associated with body weight gain and feed intake identified by meta-analysis of the mesenteric fat from crossbred beef steers. PLoS ONE 15(1): e0227154. https://

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“…For example, RNA-seq indicated a 72-fold increase of the PTAFR gene in the A549/DDP cells. It has been reported that activated PTAFR-dependent pathways in tumor cells affect the tumor microenvironment and the phenotype of the tumor-associated macrophages to promote tumor growth 90 , 91 . Of note, we did not find any previous study on PTAFR’s regulatory effect on A549/DDP cells.…”

Section: Discussionmentioning

confidence: 99%

Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance

Hossian

Zahra

Poudel

et al. 2021

Sci Rep

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This study aims to identify pathway involvement in the development of cisplatin (cis-diamminedichloroplatinum (II); CDDP) resistance in A549 lung cancer (LC) cells by utilizing advanced bioinformatics software. We developed CDDP-resistant A549 (A549/DDP) cells through prolonged incubation with the drug and performed RNA-seq on RNA extracts to determine differential mRNA and miRNA expression between A549/DDP and A549 cells. We analyzed the gene dysregulation with Ingenuity Pathway Analysis (IPA; QIAGEN) software. In contrast to prior research, which relied on the clustering of dysregulated genes to pathways as an indication of pathway activity, we utilized the IPA software for the dynamic evaluation of pathway activity depending on the gene dysregulation levels. We predicted 15 pathways significantly contributing to the chemoresistance, with several of them to have not been previously reported or analyzed in detail. Among them, the PKR signaling, cholesterol biosynthesis, and TEC signaling pathways are included, as well as genes, such as PIK3R3, miR-34c-5p, and MDM2, among others. We also provide a preliminary analysis of SNPs and indels, present exclusively in A549/DDP cells. This study's results provide novel potential mechanisms and molecular targets that can be explored in future studies and assist in improving the understanding of the chemoresistance phenotype.

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Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Cited by 17 publications

References 71 publications

Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo

Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo

Genes associated with body weight gain and feed intake identified by meta-analysis of the mesenteric fat from crossbred beef steers

Advanced bioinformatic analysis and pathway prediction of NSCLC cells upon cisplatin resistance

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