Coupling live-cell imaging and isolation of the same single cell to profile the transient states of predicted drug-tolerant cells.

Cell response variability is a starting point in cancer drug resistance that has been difficult to analyze because the tolerant cell states are short lived. Here, we present fate-seq, an approach to isolate single cells in their transient states of drug sensitivity or tolerance before profiling. The drug response is predicted in live cells, which are laser-captured by microdissection before any drug-induced change can alter their states.

TRAIL receptor-induced features of epithelial-to-mesenchymal transition increase tumour phenotypic heterogeneity: potential cell survival mechanisms.

The continuing efforts to exploit the death receptor agonists, such as the tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), for cancer therapy, have largely been impaired by the anti-apoptotic and pro-survival signalling pathways leading to drug resistance. Cell migration, invasion, differentiation, immune evasion and anoikis resistance are plastic processes sharing features of the epithelial-to-mesenchymal transition (EMT) that have been shown to give cancer cells the ability to escape cell death upon cytotoxic treatments. EMT has recently been suggested to drive a heterogeneous cellular environment that appears favourable for tumour progression.

Profiling the Non-genetic Origins of Cancer Drug Resistance with a Single-Cell Functional Genomics Approach Using Predictive Cell Dynamics.

Non-genetic heterogeneity observed in clonal cell populations is an immediate cause of drug resistance that remains challenging to profile because of its transient nature. Here, we coupled three single-cell technologies to link the predicted drug response of a cell to its own genome-wide transcriptomic profile. As a proof of principle, we analyzed the response to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) in HeLa cells to demonstrate that cell dynamics can discriminate the transient transcriptional states at the origin of cell decisions such as sensitivity and resistance.

A simple GC-MS method for the determination of diphenylamine, tolylfluanid propargite and phosalone in liver fractions.

In this study, an accurate and robust gas chromatography/mass spectrometry method was developed for quantitative analysis of diphenylamine, tolylfluanid, propargite and phosalone in liver fractions. Different injector parameters were optimized by an experimental design technique (central composite design). An optimal combination of injector temperature (°C), splitless time (min) and overpressure (kPa) values enabled to maximize the chromatographic responses.

An accurate and robust LC-MS/MS method for the quantification of chlorfenvinphos, ethion and linuron in liver samples.

A method for the determination of chlorfenvinphos, ethion and linuron in liver samples by LC-MS/MS is described. Sample treatment was performed by using Sola™ polymeric reverse phase SPE cartridges after protein precipitation. Gradient elution using 10 mM ammonium formate in methanol (A) and 10 mM ammonium formate in water (B) was used for chromatographic separation of analytes on a Hypersil™ end-capped Gold PFP reverse phase column (100 mm × 2.

Evidence of in vitro metabolic interaction effects of a chlorfenvinphos, ethion and linuron mixture on human hepatic detoxification rates.

General population exposure to pesticides mainly occurs via food and water consumption. However, their risk assessment for regulatory purposes does not currently consider the actual co-exposure to multiple substances. To address this concern, relevant experimental studies are needed to fill the lack of data concerning effects of mixture on human health.

Effect of Brewing Duration on the Antioxidant and Hepatoprotective Abilities of Tea Phenolic and Alkaloid Compounds in a t-BHP Oxidative Stress-Induced Rat Hepatocyte Model.

Tea is an interesting source of antioxidants capable of counteracting the oxidative stress implicated in liver diseases. We investigated the impact of antioxidant molecules provided by a mixture of teas' leaves (green, oolong, pu-erh) after different infusion durations in the prevention of oxidative stress in isolated rat hepatocytes, by comparison with pure epigallocatechin-3-gallate (EGCG), the main representative of tea catechins. Dried aqueous tea extracts (ATE) obtained after 5, 15 and 30 min infusion time were characterized for total polyphenols (gallic acid equivalent), catechins, gallic acid and caffeine (HPLC-DAD/ESI-MS) contents, and for scavenging ability against 2,2-diphenyl-1-picrylhydrazyl free radical.

Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function? An in vitro study.

As bisphenol A (BPA) has been shown to induce adverse effects on human health, especially through the activation of endocrine pathways, it is about to be withdrawn from the European market and replaced by analogues such as bisphenol S (BPS). However, toxicological data on BPS is scarce, and so it is necessary to evaluate the possible effects of this compound on human health. We compared the effect of BPA and BPS on obesity and hepatic steatosis processes using low doses in the same range as those found in the environment.

Comparative study of bisphenol A and its analogue bisphenol S on human hepatic cells: a focus on their potential involvement in nonalcoholic fatty liver disease.

For several decades, people have been in contact with bisphenol A (BPA) primarily through their diet. Nowadays it is gradually replaced by an analogue, bisphenol S (BPS). In this study, we compared the effects of these two bisphenols in parallel with the positive control diethylstilbestrol (DES) on different hepatocyte cell lines.

Atrazine represses S100A4 gene expression and TPA-induced motility in HepG2 cells.

Atrazine (ATZ) is probably the most widely used herbicide in the world. However there are still many controversies regarding its impacts on human health. Our investigations on the role of pesticides in liver dysfunctions have led us to detect an inhibition of FSP1 expression of 70% at 50μm and around 95% at 500μM of ATZ (p<0.

Crosstalk between beta-catenin and snail in the induction of epithelial to mesenchymal transition in hepatocarcinoma: role of the ERK1/2 pathway.

Epithelial to mesenchymal transition (EMT) is an integral process in the progression of many epithelial tumors. It involves a coordinated series of events, leading to the loss of epithelial features and the acquisition of a mesenchymal phenotype, resulting in invasion and metastasis. The EMT of hepatocellular carcinoma (HCC) cells is thought to be a key event in intrahepatic dissemination and distal metastasis.

Organochlorine pesticides induce epithelial to mesenchymal transition of human primary cultured hepatocytes.

Persistent organic pollutants (POPs) are a group of organic or chemicals that adversely affect human health and are persistent in the environment. These highly toxic compounds include industrial chemicals, pesticides such as organochlorines, and unwanted wastes such as dioxins. Although studies have described the general toxicity effects of organochlorine pesticides, the mechanisms underlying its potential carcinogenic effects in the liver are not well understood.

Effects of endosulfan on hepatoma cell adhesion: Epithelial-mesenchymal transition and anoikis resistance.

Endosulfan is an organochlorine pesticide commonly used in agriculture yet classified by the Stockholm Convention in 2011 as a persistent organic pollutant (POP). Its potential toxicity makes its continued use a major public health concern. Despite studies in laboratory animals, the molecular mechanisms underlying the carcinogenic effects of endosulfan in human liver remain poorly understood.

On the use of ultrasounds to quantify the longitudinal threshold force to detach osteoblastic cells from a conditioned glass substrate.

Cell adhesion on a biomaterial is an important phase of the cell-material interactions and the quality of this phase governs the success of the biomaterial integration. Understanding of the phenomena of cell adhesion and in particular understanding of cell adhesion on biomaterials is of crucial importance for the development of new biomaterials with excellent biocompatibility. One of the physical quantitative indexes to evaluate the quality of cell-material adhesion is its strength.