scholarly journals In Vitro Cell Sensitivity to Palytoxin Correlates with High Gene Expression of the Na+/K+-ATPase β2 Subunit Isoform

2020 ◽  
Vol 21 (16) ◽  
pp. 5833
Author(s):  
Marco Pelin ◽  
Gabriele Stocco ◽  
Chiara Florio ◽  
Silvio Sosa ◽  
Aurelia Tubaro
Keyword(s):  
Gene Expression ◽  
Interquartile Range ◽  
Toxic Effects ◽  
Maximum Effect ◽  
Molecular Evidence ◽  
Expression Ratio ◽  
Assay Sensitivity ◽  
High Gene Expression ◽  
High Gene

The marine polyether palytoxin (PLTX) is one of the most toxic natural compounds, and is involved in human poisonings after oral, inhalation, skin and/or ocular exposure. Epidemiological and molecular evidence suggest different inter-individual sensitivities to its toxic effects, possibly related to genetic-dependent differences in the expression of Na+/K+-ATPase, its molecular target. To identify Na+/K+-ATPase subunits, isoforms correlated with in vitro PLTX cytotoxic potency, sensitivity parameters (EC50: PLTX concentration reducing cell viability by 50%; Emax: maximum effect induced by the highest toxin concentration; 10−7 M) were assessed in 60 healthy donors’ monocytes by the MTT (methylthiazolyl tetrazolium) assay. Sensitivity parameters, not correlated with donors’ demographic variables (gender, age and blood group), demonstrated a high inter-individual variability (median EC50 = 2.7 × 10−10 M, interquartile range: 0.4–13.2 × 10−10 M; median Emax = 92.0%, interquartile range: 87.5–94.4%). Spearman’s analysis showed significant positive correlations between the β2-encoding ATP1B2 gene expression and Emax values (rho = 0.30; p = 0.025) and between Emax and the ATP1B2/ATP1B3 expression ratio (rho = 0.38; p = 0.004), as well as a significant negative correlation between Emax and the ATP1B1/ATP1B2 expression ratio (rho = −0.30; p = 0.026). This toxicogenetic study represents the first approach to define genetic risk factors that may influence the onset of adverse effects in human PLTX poisonings, suggesting that individuals with high gene expression pattern of the Na+/K+-ATPase β2 subunit (alone or as β2/β1 and/or β2/β3 ratio) could be highly sensitive to PLTX toxic effects.

scholarly journals MCT1 is a Predictive Marker for Lenalidomide Maintenance Therapy in Multiple Myeloma

2021 ◽  
Author(s):  
Jacob Stroh ◽  
Anja Seckinger ◽  
Michael Heider ◽  
Martina Rudelius ◽  
Ruth Eichner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Xenograft Model ◽  
Predictive Marker ◽  
Bortezomib Treatment ◽  
High Gene Expression ◽  
Cd147 Expression ◽  
High Gene

Biomarkers that predict response to lenalidomide maintenance therapy in patients with multiple myeloma (MM) have remained elusive. We have shown that IMiDs exert anti-MM activity via destabilization of MCT1 and CD147. Here, samples of 654 patients receiving lenalidomide (n=455), thalidomide (n=98) or bortezomib (n=101) maintenance were assessed using gene expression profiling and RNA-sequencing, followed by correlation of MCT1 and CD147 expression with progression-free (PFS) and overall survival (OS) data. Patients with high gene expression levels of MCT1 showed significantly reduced PFS (31.9 vs. 48.2 months in MCT1high vs. MCT1low, P=.03) and OS (75.9 months vs. not reached (NR) months in MCT1high vs. MCT1low; P=.001) in case of lenalidomide maintenance, whereas MCT1 expression had no significant impact on PFS or OS in patients with bortezomib maintenance. We validated the predictive role of MCT1 for IMiD-based maintenance in an independent cohort of patients receiving thalidomide (OS 83.6 months vs. NR in MCT1high vs. MCT1low; P=.03). Functional validation showed that MCT1 overexpression in human MM cell lines significantly reduced efficacy of lenalidomide, while no change was observed upon bortezomib treatment, both in vitro and in an MM xenograft model. Together, we establish MCT1-expression as a predictive marker for response to lenalidomide-based maintenance treatment.

scholarly journals Retained Heterodisomy Is Associated with High Gene Expression in Hyperhaploid Inflammatory Leiomyosarcoma

Neoplasia ◽  
2012 ◽  
Vol 14 (9) ◽  
pp. 807-IN5 ◽  
Author(s):  
Karolin H. Nord ◽  
Kajsa Paulsson ◽  
Srinivas Veerla ◽  
Johan Wejde ◽  
Otte Brosjö ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Gene Expression ◽  
High Gene

Exertional heat injury and gene expression changes: a DNA microarray analysis study

2004 ◽  
Vol 96 (5) ◽  
pp. 1943-1953 ◽  
Author(s):  
Larry A. Sonna ◽  
C. Bruce Wenger ◽  
Scott Flinn ◽  
Holly K. Sheldon ◽  
Michael N. Sawka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Evidence ◽  
Peripheral Blood Mononuclear ◽  
Heat Injury ◽  
Shock Proteins

This study examined gene expression changes associated with exertional heat injury (EHI) in vivo and compared these changes to in vitro heat shock responses previously reported by our laboratory. Peripheral blood mononuclear cell (PBMC) RNA was obtained from four male Marine recruits (ages 17-19 yr) who presented with symptoms consistent with EHI, core temperatures ranging from 39.3 to 42.5°C, and elevations in serum enzymes such as creatine kinase. Controls were age- and gender-matched Marines from whom samples were obtained before and several days after an intense field-training exercise in the heat (“The Crucible”). Expression analysis was performed on Affymetrix arrays (containing ∼12,600 sequences) from pooled samples obtained at three times for EHI group (at presentation, 2-3 h after cooling, and 1-2 days later) and compared with control values (average signals from two chips representing pre- and post-Crucible samples). After post hoc filtering, the analysis identified 361 transcripts that had twofold or greater increases in expression at one or more of the time points assayed and 331 transcripts that had twofold or greater decreases in expression. The affected transcripts included sequences previously shown to be heat-shock responsive in PBMCs in vitro (including both heat shock proteins and non-heat shock proteins), a number of sequences whose changes in expression had not previously been noted as a result of in vitro heat shock in PBMCs (including several interferon-induced sequences), and several nonspecific stress response genes (including ubiquitin C and dual-specificity phosphatase-1). We conclude that EHI produces a broad stress response that is detectable in PBMCs and that heat stress per se can only account for some of the observed changes in transcript expression. The molecular evidence from these patients is thus consistent with the hypothesis that EHI can result from cumulative effects of multiple adverse interacting stimuli.

scholarly journals High gene expression of semaphorin 5A in pancreatic cancer is associated with tumor growth, invasion and metastasis

2010 ◽  
Vol 127 (6) ◽  
pp. 1373-1383 ◽  
Author(s):  
Anguraj Sadanandam ◽  
Michelle L. Varney ◽  
Seema Singh ◽  
Abdelkader E. Ashour ◽  
Nicolas Moniaux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Invasion And Metastasis ◽  
High Gene Expression ◽  
High Gene ◽  
Semaphorin 5A

scholarly journals Meta-analysis of human methylomes reveals stably methylated sequences surrounding CpG islands associated with high gene expression

2014 ◽  
Vol 7 (1) ◽  
pp. 28 ◽  
Author(s):  
Rachel Edgar ◽  
Powell Patrick Tan ◽  
Elodie Portales-Casamar ◽  
Paul Pavlidis
Keyword(s):  
Gene Expression ◽  
Meta Analysis ◽  
Cpg Islands ◽  
High Gene Expression ◽  
High Gene
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