scholarly journals Attomole-per Cell Atomic Mass Spectrometry Measurement of Platinum and Gold Drugs in Cultured Lung Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7627
Author(s):  
Wioletta Jakubczak ◽  
Maja Haczyk-Więcek ◽  
Katarzyna Pawlak
Keyword(s):  
Metal Ions ◽  
Inductively Coupled Plasma ◽  
Small Cell Lung Carcinoma ◽  
Cross Flow ◽  
Transition Metal Ions ◽  
Normal Lung ◽  
Lower Efficiency ◽  
Cell Lung Carcinoma ◽  
Drug Concentrations ◽  
Inhibitory Drug

In this study, we developed a strategy to determine atto- and femtomolar amounts of metal ions in lysates and mineralizates of cells (human non-small-cell lung carcinoma (NSCLC, A549) and normal lung (MRC-5)) exposed to cytotoxic metallo-drugs: cisplatin and auranofin at concentrations close to the half-maximal inhibitory drug concentrations (IC50). The developed strategy combines data obtained using biological and chemical approaches. Cell density was determined using two independent cell staining assays using trypan blue, calcein AM/propidium iodide. Metal concentrations in lysed and mineralized cells were established employing a mass spectrometer with inductively coupled plasma (ICP-MS) and equipped with a cross-flow nebulizer working in aspiration mode. It allowed for detecting of less than 1 fg of metal per cell. To decrease the required amount of sample material (from 1.5 mL to ~100 µL) without loss of sensitivity, the sample was introduced as a narrow band into a constant stream of liquid (flow-injection analysis). It was noticed that the selectivity of cisplatin accumulation by cells depends on the incubation time. This complex is accumulated by cells at a lower efficiency than auranofin and is found primarily in the lysate representing the cytosol. In contrast, auranofin interacts with water-insoluble compounds. Despite their different mechanism of action, both metallo-drugs increased the accumulation of transition metal ions responsible for oxidative stress.

scholarly journals LETM1 is a potential biomarker of prognosis in lung non-small cell carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Longzhen Piao ◽  
Zhaoting Yang ◽  
Ying Feng ◽  
Chengye Zhang ◽  
Chunai Cui ◽  
...  
Keyword(s):  
Cox Regression ◽  
Transmembrane Protein ◽  
Small Cell Lung Carcinoma ◽  
Clinical Stage ◽  
Small Cell ◽  
Cancer Prognosis ◽  
Normal Lung ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis ◽  
Potential Biomarker

Abstract Background Although the leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1) is one of the mitochondrial inner membrane proteins that is involved in cancer prognosis in various tumors, LETM1 as a biomarker for prognostic evaluation of non-small cell lung carcinoma (NSCLC) has not been well studied. Methods To address this issue, we used 75 cases NSCLC, 20 cases adjacent normal lung tissues and NSCLC cell lines. We performed immunohistochemistry staining and western blot analysis as well as immunofluorescence imaging. Results Our studies show that expression of LETM1 is significantly correlated with the lymph node metastasis (p = 0.003) and the clinical stage (p = 0.005) of NSCLC. The Kaplan-Meier survival analysis revealed that NSCLC patients with positive expression of LETM1 exhibits a shorter overall survival (OS) rate (p = 0.005). The univariate and multivariate Cox regression analysis indicated that LETM1 is a independent poor prognostic marker of NSCLC. In addition, the LETM1 expression is correlated with cancer stemness-related gene LGR5 (p < 0.001) and HIF1α expression (p < 0.001), but not with others. Moreover, LETM1 expression was associated with the expression of cyclin D1 (p = 0.003), p27 (p = 0.001), pPI3K(p85) (p = 0.025), and pAkt-Thr308 (p = 0.004). Further, our studies show in LETM1-positive NSCLC tissues the microvessel density was significantly higher than in the negative ones (p = 0.024). Conclusion These results indicate that LETM1 is a potential prognostic biomarker of NSCLC.

scholarly journals miR-190, CDK1, MCM10 and NDC80 predict the prognosis of the patients with lung cancer

2019 ◽  
Vol 27 (1) ◽  
pp. 15-24
Author(s):  
Li-Wei Gao ◽  
Guo-Liang Wang
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Normal Lung ◽  
Ppi Network ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Network Modules ◽  
Tcga Dataset

Abstract Lung cancer (LC), which includes small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), is common and has a high fatality rate. This study aimed to reveal the prognostic mechanisms of LC. GSE30219 was extracted from the Gene Expression Omnibus (GEO) database, and included 293 LC samples and 14 normal lung samples. Differentially expressed genes (DEGs) were identified using the Limma package, and subjected to pathway enrichment analysis using DAVID. MicroRNAs (miRNAs) targeting the DEGs were predicted using Webgestalt. Cytoscape software was used to build a protein-protein interaction (PPI) network and to identify significant network modules. Survival analysis was conducted using Survminer and Survival packages, and validation was performed using The Cancer Genome Atlas (TCGA) dataset. The good and poor prognosis groups contained 518 DEGs. miR-190, miR-493, and miR-218 for the upregulated genes and miR-302, miR-200, and miR-26 for the downregulated genes were predicted. Three network modules (module 1, 2, and 3) were identified from the PPI network. CDK1, MCM10, and NDC80 were the core nodes of module 1, 2, and 3, respectively. In module 1, CDK1 interacted with both CCNB1 and CCNB2. Additionally, CDK1, CCNB1, CCNB2, MCM10, and NDC80 expression levels correlated with clinical survival and were identified as DEGs in both GSE30219 and the TCGA dataset. miR-190, miR-493, miR-218, miR-200, and miR-302 might act in LC by targeting the DEGs. CDK1, CCNB1, CCNB2, MCM10, and NDC80 might also influence the prognosis of LC.

scholarly journals Protein Binding of a Novel Platinum-Based Anticancer Agent BP-C1 Containing a Lignin-Derived Polymeric Ligand

2021 ◽  
Vol 11 (22) ◽  
pp. 11008
Author(s):  
Elena Fedoros ◽  
Sergey Pigarev ◽  
Natalya Ivanenko ◽  
Megan Westbury ◽  
Nikolay Solovyev
Keyword(s):  
Protein Binding ◽  
Inductively Coupled Plasma ◽  
Ex Vivo ◽  
Small Cell Lung Carcinoma ◽  
Equilibrium Dialysis ◽  
Microwave Digestion ◽  
Antineoplastic Agent ◽  
Cell Lung Carcinoma ◽  
Polycarboxylic Acids ◽  
Polymeric Ligand

Platinum (Pt) antineoplastic agents remain indispensable for the treatment of oncological disease. Pt-based drugs are mainly used in the therapy of ovarian cancer and non-small-cell lung carcinoma. A novel platinum-containing antineoplastic agent BP-C1 is a complex of diamminoplatinum with an oxygen-donor polymeric ligand of benzene-polycarboxylic acids, isolated from natural lignin. The aim of the study was to investigate ex vivo protein binding of BP-C1. Protein binding of BP-C1 was tested using equilibrium dialysis. Pooled blood plasma was used in the study. Control solutions contained the same dosages of BP-C1 in PBS (pH 7.2). Plasma and control solutions were submitted to equilibrium dialysis across a vertical 8 kDa cut-off membrane for 4 h at 37 °C under gentle shaking. Platinum was quantified in dialysis and retained fractions using inductively coupled plasma mass spectrometry after microwave digestion. The dialysis system was tested and validated; this showed no protein saturation with platinum. A medium degree of binding of platinum to macromolecular species of ca. 60% was observed. The study showed the maintenance of a high fraction of free BP-C1 in the bloodstream, facilitating its pharmacological activity.

scholarly journals Flavoured water consumption alters pharmacokinetic parameters and increases exposure of erlotinib and gefitinib in a preclinical study using Wistar rats

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9881
Author(s):  
Aliyah Almomen ◽  
Hadir M. Maher ◽  
Nourah Z. Alzoman ◽  
Shereen M. Shehata ◽  
Amal Alsubaie
Keyword(s):  
Wistar Rats ◽  
Drug Exposure ◽  
Small Cell Lung Carcinoma ◽  
Clinical Importance ◽  
Pharmacokinetic Parameters ◽  
Oral Clearance ◽  
Cell Lung Carcinoma ◽  
Transporter Proteins ◽  
Apparent Oral Clearance ◽  
Drug Concentrations

Background Erlotinib (ERL) and Gefitinib (GEF) are considered first line therapy for the management of non-small cell lung carcinoma (NSCLC). Like other tyrosine kinase inhibitors (TKIs), ERL and GEF are mainly metabolized by the cytochrome P450 (CYP450) CYP3A4 isoform and are substrates for transporter proteins with marked inter-/intra-individual pharmacokinetic (PK) variability. Therefore, ERL and GEF are candidates for drug-drug and food-drug interactions with a consequent effect on drug exposure and/or drug-related toxicities. In recent years, the consumption of flavoured water (FW) has gained in popularity. Among multiple ingredients, fruit extracts, which might constitute bioactive flavonoids, can possess an inhibitory effect on the CYP450 enzymes or transporter proteins. Therefore, in this study we investigated the effects of different types of FW on the PK parameters of ERL and GEF in Wistar rats. Methods ERL and GEF PK parameters in different groups of rats after four weeks consumption of different flavours of FW, namely berry, peach, lime, and pineapple, were determined from plasma drug concentrations using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Results Data indicated that tested FWs altered the PK parameters of both ERL and GEF differently. Lime water had the highest impact on most of ERL and GEF PK parameters, with a significant increase in Cmax (95% for ERL, 58% for GEF), AUC0–48 (111% for ERL, 203% for GEF), and AUC0–∞ (200% for ERL, 203% for GEF), along with a significant decrease in the apparent oral clearance of both drugs (65% for ERL, 67% for GEF). The order by which FW affected the PK parameters for ERL and GEF was as follows: lime > pineapple > berry > peach. Conclusion The present study indicates that drinking FW could be of significance in rats receiving ERL or GEF. Our results indicate that the alteration in PKs was mostly recorded with lime, resulting in an enhanced bioavailability, and reduced apparent oral clearance of the drugs. Peach FW had a minimum effect on the PK parameters of ERL and no significant effect on GEF PKs. Accordingly, it might be of clinical importance to evaluate the PK parameters of ERL and GEF in human subjects who consume FW while receiving therapy.

scholarly journals Selective separation of some ecotoxic transition metal ions from aqueous solutions using immobilized macrocyclic material containing solid phase extraction system

2011 ◽  
Vol 9 (6) ◽  
pp. 1019-1026 ◽  
Author(s):  
Ismail Rahman ◽  
Yoshiaki Furusho ◽  
Zinnat Begum ◽  
Akhmad Sabarudin ◽  
Shoji Motomizu ◽  
...  
Keyword(s):  
Transition Metal ◽  
Solid Phase Extraction ◽  
Metal Ions ◽  
Water Samples ◽  
Inductively Coupled Plasma ◽  
Solid Phase ◽  
Transition Metal Ions ◽  
Phase Extraction ◽  
Inductively Coupled ◽  
Ion Extraction

AbstractA simple flow-based method was developed for the simultaneous separation of certain transition metal ions (Co, Ni, Cu, Zn, Cd) from aqueous systems, which ions show ecotoxic effects when present at elevated concentrations. A silica-gel-bonded macrocycle system, commonly known as molecular recognition technology (MRT) gel, was used for solid phase extraction (SPE) of the target analytes. The collection behavior of the MRT-SPE system was studied based on pH. Fortified deionized water samples containing 250 µg L−1 of each of the elements were treated at the flow rate of 1 mL min−1. The collected analytes were then eluted by 3 M HNO3 and analyzed using inductively coupled plasma spectrometry. Detection limits of the proposed technique were in the range of 0.004–0.040 µg L−1 for the studied metal ions. The validity of this separation technique was checked with spiked ‘real’ water samples, which produced satisfactory recoveries of 96–102%. The non-destructive nature and highly selective ion-extraction capability of the SPE material are the most important aspects of the proposed method and they are the main focus of this paper.

Basic Helix-Loop-Helix Transcription Factor Profiling of Lung Tumors Shows Aberrant Expression of the Proneural Gene Atonal Homolog 1 (ATOH1, HATH1, MATH1) in Neuroendocrine Tumors

2007 ◽  
Vol 22 (2) ◽  
pp. 114-123 ◽  
Author(s):  
B.A. Westerman ◽  
R.H.J. Breuer ◽  
A. Poutsma ◽  
A. Chhatta ◽  
L.A. Noorduyn ◽  
...  
Keyword(s):  
Small Cell Lung Carcinoma ◽  
Lung Tumors ◽  
Normal Lung ◽  
Aberrant Expression ◽  
Cell Lung Carcinoma ◽  
Basic Helix Loop Helix ◽  
Neuroendocrine Markers ◽  
Helix Loop Helix ◽  
Bhlh Genes ◽  
Lung Malignancies

Microarray-based expression profiling studies of lung adenocarcinomas have defined neuroendocrine subclasses with poor prognosis. As neuroendocrine development is regulated by members of the achaetescute and atonal classes of basic helix-loop-helix (bHLH) transcription factors, we analyzed lung tumors for expression of these factors. Out of 13 bHLH genes tested, 4 genes, i.e., achaetescute complex-like 1 (ASCL1, HASH1, Mash1), atonal homolog 1 (ATOH1, HATH1, MATH1), NEUROD4 (ATH-3, Atoh3, MATH-3) and neurogenic differentiation factor 1 (NEUROD1, NEUROD, BE-TA2), showed differential expression among lung tumors and absent or low expression in normal lung. As expected, tumors that have high levels of ASCL1 also express neuroendocrine markers, and we found that this is accompanied by increased levels of NEUROD1. In addition, we found ATOH1 expression in 9 (16%) out of 56 analyzed adenocarcinomas and these tumors showed neuroendocrine features as shown by dopa decarboxylase mRNA expression and immunostaining for neuroendocrine markers. ATOH1 expression as well as NEUROD4 was observed in small cell lung carcinoma (SCLC), a known neuroendocrine tumor. Since ATOH1 is not known to be involved in normal lung development, our results suggest that aberrant activation of ATOH1 leads to a neuroendocrine phenotype similar to what is observed for ASCL1 activation during normal neuroendocrine development and in lung malignancies. Our preliminary data indicate that patients with ATOH1-expressing adenocarcinomas might have a worse prognosis.

HREM Study of electron-induced surface radiation damage in ReO3

1991 ◽  
Vol 49 ◽  
pp. 636-637
Author(s):  
R. Ai ◽  
H.-J. Fan ◽  
L. D. Marks
Keyword(s):  
Transition Metal ◽  
Metal Ions ◽  
Metal Oxides ◽  
Electron Irradiation ◽  
Transition Metal Oxides ◽  
Carbon Film ◽  
Transition Metal Ions ◽  
Surface Radiation ◽  
Valence Transition ◽  
Electron Microscopes

It has been known for a long time that electron irradiation induces damage in maximal valence transition metal oxides such as TiO2, V2O5, and WO3, of which transition metal ions have an empty d-shell. This type of damage is excited by electronic transition and can be explained by the Knoteck-Feibelman mechanism (K-F mechanism). Although the K-F mechanism predicts that no damage should occur in transition metal oxides of which the transition metal ions have a partially filled d-shell, namely submaximal valence transition metal oxides, our recent study on ReO3 shows that submaximal valence transition metal oxides undergo damage during electron irradiation.ReO3 has a nearly cubic structure and contains a single unit in its cell: a = 3.73 Å, and α = 89°34'. TEM specimens were prepared by depositing dry powders onto a holey carbon film supported on a copper grid. Specimens were examined in Hitachi H-9000 and UHV H-9000 electron microscopes both operated at 300 keV accelerating voltage. The electron beam flux was maintained at about 10 A/cm2 during the observation.

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