6-Polyaminosteroid Squalamine Analogues Display Antibacterial Activity against Resistant Pathogens.

A series of 6-polyaminosteroid analogues of squalamine were synthesized with moderate to good yields and evaluated for their antimicrobial properties against both susceptible and resistant Gram-positive (vancomycin-resistant and methicillin-resistant ) and Gram-negative (carbapenem-resistant and bacterial strains. Minimum inhibitory concentrations against Gram-positive bacteria ranged from 4 to 16 µg/mL for the most effective compounds, and , and showed an additive or synergistic effect with vancomycin or oxacillin. On the other hand, the derivative , which carries a spermine moiety like that of the natural trodusquemine molecule, was found to be the most active derivative against all the resistant Gram-negative bacteria tested, with an MIC value of 16 µg/mL.

Blood contamination of the pharmaceutical staff by irinotecan and its two major metabolites inside and outside a compounding unit.

Background: Caregivers in healthcare settings are exposed to a risk of antineoplastic drug contamination which can lead to adverse health effects. Biological monitoring is necessary to estimate the actual level of exposure of these workers. This study was conducted with the aim of assessing blood contamination levels by irinotecan and its metabolites of pharmaceutical staff operating inside and outside a compounding unit.

Differential normal skin transcriptomic response in total body irradiated mice exposed to scattered versus scanned proton beams.

Proton therapy allows to avoid excess radiation dose on normal tissues. However, there are some limitations. Indeed, passive delivery of proton beams results in an increase in the lateral dose upstream of the tumor and active scanning leads to strong differences in dose delivery.

Biological Effects of Scattered Versus Scanned Proton Beams on Normal Tissues in Total Body Irradiated Mice: Survival, Genotoxicity, Oxidative Stress and Inflammation.

Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both modalities of proton beam delivery on blood; skin; lung and heart in a murine model.

Comparative study on gene expression profile in rat lung after repeated exposure to diesel and biodiesel exhausts upstream and downstream of a particle filter.

Biodiesel is considered as a valuable and less toxic alternative to diesel. However, cellular and molecular effects of repeated exposure to biodiesel emissions from a recent engine equipped with a diesel particle filter (DPF) remain to be characterized. To gain insights about this point, the lung transcriptional signatures were analyzed for rats (n = 6 per group) exposed to filtered air, 30% rapeseed biodiesel (B30) blend or reference diesel (RF0), upstream and downstream a DPF, for 3 weeks (3 h/day, 5 days/week).

Nitrogen Dioxide Inhalation Exposures Induce Cardiac Mitochondrial Reactive Oxygen Species Production, Impair Mitochondrial Function and Promote Coronary Endothelial Dysfunction.

Traffic air pollution is a major health problem and is recognized as an important risk factor for cardiovascular (CV) diseases. In a previous experimental study, we showed that diesel exhaust (DE) exposures induced cardiac mitochondrial and CV dysfunctions associated with the gaseous phase. Here, we hypothesized that NO exposures to levels close to those found in DE induce a mitochondrial reactive oxygen species (ROS) production, which contribute to an endothelial dysfunction, an early indicator for numerous CV diseases.

The Possibility of Using Genotoxicity, Oxidative Stress and Inflammation Blood Biomarkers to Predict the Occurrence of Late Cutaneous Side Effects after Radiotherapy.

Despite the progresses performed in the field of radiotherapy, toxicity to the healthy tissues remains a major limiting factor. The aim of this work was to highlight blood biomarkers whose variations could predict the occurrence of late cutaneous side effects. Two groups of nine patients treated for Merkel Cell Carcinoma (MCC) were established according to the grade of late skin toxicity after adjuvant irradiation for MCC: grade 0, 1 or 2 and grade 3 or 4 of RTOG (Radiation Therapy Oncology Group)/EORTC (European Organization for Research and Treatment of Cancer).

Hadrontherapy Interactions in Molecular and Cellular Biology.

The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues.

[Cardiac complications of breast radiation therapy].

Adjuvant radiation therapy in breast cancer is a standard of care, either post-lumpectomy or in case of lymph node involvement. Internal mammary chain (IMC) is more and more included in the clinical target volume, because it increases overall survival. This increase must be weighed against cardiac complications in left breast cancer.

An integrated functional and transcriptomic analysis reveals that repeated exposure to diesel exhaust induces sustained mitochondrial and cardiac dysfunctions.

Diesel exhaust (DE) contributes to air pollution, an important risk factor for cardiovascular diseases. However, the mechanisms by which DE exposure induces cardiovascular dysfunction remain unknown and there is still debate on the contribution of the primary particulate matter (PM) fraction compared to the gaseous phase. Although the mitochondria play a key role in the events leading to cardiovascular diseases, their role in DE-induced cardiovascular effects has not been investigated.

Chemical characterization of fine and ultrafine PM, direct and indirect genotoxicity of PM and their organic extracts on pulmonary cells.

Particulate matter in ambient air constitutes a complex mixture of fine and ultrafine particles composed of various chemical compounds including metals, ions, and organics. A multidisciplinary approach was developed by studying physico-chemical characteristics and mechanisms involved in the toxicity of particulate atmospheric pollution. PM and PM including ultrafine particles were sampled in Dunkerque, a French industrialized seaside city.

Influence of aging in the modulation of epigenetic biomarkers of carcinogenesis after exposure to air pollution.

Background: Classified as carcinogenic to humans by the IARC in 2013, fine air particulate matter (PM) can be inhaled and retained into the lung or reach the systemic circulation. This can cause or exacerbate numerous pathologies to which the elderly are often more sensitive.

Methods: In order to estimate the influence of age on the development of early cellular epigenetic alterations involved in carcinogenesis, peripheral blood mononuclear cells sampled from 90 patients from three age classes (25-30, 50-55 and 75-80 years old) were ex vivo exposed to urban PM.

Comparative study of diesel and biodiesel exhausts on lung oxidative stress and genotoxicity in rats.

The contribution of diesel exhaust to atmospheric pollution is a major concern for public health, especially in terms of occurrence of lung cancers. The present study aimed at addressing the toxic effects of a repeated exposure to these emissions in an animal study performed under strictly controlled conditions. Rats were repeatedly exposed to the exhaust of diesel engine.

Is hyperthermic intraperitoneal chemotherapy (HIPEC) safe for healthcare workers?

Background: During hyperthermic intraperitoneal chemotherapy (HIPEC), caregivers are exposed by different routes to cytotoxic drugs. This review proposes an overview of the safety of HIPEC by assessing existing data on protection procedures, biological and non-biological samples. Based on these data, relevant good practices, eventual irrelevant overprotection procedures and missing data to implement adapted protections are highlighted.

Impact of after-treatment devices and biofuels on diesel exhausts genotoxicity in A549 cells exposed at air-liquid interface.

Using an air-liquid interface (ALI) device in dynamic conditions, we evaluated the efficiency of fuel after-treatment strategies (diesel oxidation catalysis, DOC, and diesel particulate filter, DPF, devices) and the impact of 7% and 30% rapeseed methyl esters (RME) blending on oxidative stress and genotoxicity induced in A549 lung cells after 3h exposure to whole Diesel exhausts. Oxidative stress was studied using assays of ROS production, glutathione level, catalase and superoxide-dismutase (SOD) activities. No oxidative stress and no clear differences on cytotoxicity patterns between biodiesel and standard Diesel exhausts were found.

Cytotoxicity and genotoxicity effects of arsenic trioxide on SQ20B human laryngeal carcinoma cells.

This study investigates the cytotoxicity and the genotoxicity induced by arsenic trioxide AsOin human laryngeal SQ20B carcinoma cell line. SQ20B cells were exposed to graded concentrations of arsenic trioxide (2 and 5μM) for 48h. Comet assay and γ-H2AX foci formation were used for measuring DNA damages, flow cytometry was used to identify cell cycle alterations and apoptosis, while cell morphology was visualized using transmission electron microscopy.

Fine and ultrafine atmospheric particulate matter at a multi-influenced urban site: Physicochemical characterization, mutagenicity and cytotoxicity.

Particulate Matter (PM) air pollution is one of the major concerns for environment and health. Understanding the heterogeneity and complexity of fine and ultrafine PM is a fundamental issue notably for the assessment of PM toxicological effects. The aim of this study was to evaluate mutagenicity and cytotoxicity of a multi-influenced urban site PM, with or without the ultrafine fraction.

Genotoxic effects of cadmium in human head and neck cell line SQ20B.

As cadmium may be involved in the etiology of head and neck cancers, we investigated in the present work, the cytotoxic and genotoxic effects of Cd on human larynx cells. SQ20B cells were exposed to 25 and 50 μM Cd for 48 and 72 h. Results showed a dose-dependent decrease in cell viability, especially after 48 h, associated with mitochondria alterations as showed by transmission electronic microscopy.

Comparative mutagenicity and genotoxicity of particles and aerosols emitted by the combustion of standard vs. rapeseed methyl ester supplemented bio-diesel fuels: impact of after treatment devices: oxidation catalyst and particulate filter.

Diesel exhausts are partly responsible for the deleterious effects on human health associated with urban pollution, including cardiovascular diseases, asthma, COPD, and possibly lung cancer. Particulate fraction has been incriminated and thus largely investigated for its genotoxic properties, based on exposure conditions that are, however, not relevant for human risk assessment. In this paper, original and more realistic protocols were used to investigate the hazards induced by exhausts emitted by the combustion of standard (DF0) vs.

Mutagenicity and clastogenicity of native airborne particulate matter samples collected under industrial, urban or rural influence.

Airborne particulate matter has recently been classified by the IARC as carcinogenic to humans (group 1). However, the link between PM chemical composition and its carcinogenicity is still unclear. The aim of the present study was to evaluate and to compare genotoxic potencies of 6 native PM samples collected in spring-summer or autumn-winter, either in industrial, urban or rural area.

Dramatic increase in oxidative stress in carbon-irradiated normal human skin fibroblasts.

Skin complications were recently reported after carbon-ion (C-ion) radiation therapy. Oxidative stress is considered an important pathway in the appearance of late skin reactions. We evaluated oxidative stress in normal human skin fibroblasts after carbon-ion vs.

Xenobiotic metabolism induction and bulky DNA adducts generated by particulate matter pollution in BEAS-2B cell line: geographical and seasonal influence.

Airborne particulate matter (PM) toxicity is of growing interest as diesel exhaust particles have been classified as carcinogenic to humans. However, PM is a mixture of chemicals, and respective contribution of organic and inorganic fractions to PM toxicity remains unclear. Thus, we analysed the link between chemical composition of PM samples and bulky DNA adduct formation supported by CYP1A1 and 1B1 genes induction and catalytic activities.

Benzo[a]pyrene, aflatoxine B₁ and acetaldehyde mutational patterns in TP53 gene using a functional assay: relevance to human cancer aetiology.

Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B(1) exposure.