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High levels of P-glycoprotein in tumor cells of osteosarcoma appear to increase the risk of tumor relapse or death following surgery and chemotherapy. Osteosarcoma is a bone tumor that is often cancerous. Researchers studied the levels of the membrane pump P-glycoprotein in tumor cells of 92 patients with osteosarcoma who had surgery and chemotherapy. In 28 (30%) of the tumors, P-glycoprotein appeared at elevated levels in cells throughout the tumor. Tumors located at the end of bones closer to the torso tended to have higher P-glycoprotein levels. During a minimum follow-up of 63 months, the rate of tumor relapse or death during remission was 3.4 times higher in people with high P-glycoprotein levels. Poor response to chemotherapy also appeared to increase the likelihood of a poor outcome.

The communities of microorganisms and their genomes in a defined environment are collectively referred to as microbiomes (Marchesi and Ravel, 2015). They include representatives from the Bacteria, Archaea, lower and higher Eukarya, and viruses, and are found in most environments such as soils, aquatic habitats, surfaces and specific lumen of plants, animals and humans. According to ongoing studies, microbiome structures and dynamics across the food system can have both direct and indirect effects on human and animal health, in addition to their impact on food quality, safety and sustainability (CNBBSV concept paper, 2019). Moreover, recent research projects have offered new insights into the associations between microbiomes and a wide range of human diseases as well as their possible impact in modulating the exposure to environmental chemicals. As one of the core tasks of EFSA is to assess risks to human and animal health and/or the environment from substances linked to food and feed production, the increasing understanding of the role of microbiomes in health calls for a prospective mapping of their roles into regulatory scientific assessment processes with a view to understanding their potential health impact. [ABSTRACT FROM AUTHOR]

This document describes the lifecycle of cross‐cutting guidance documents in EFSA. Cross‐cutting guidance documents deal with matters of a horizontal nature in fields that affect scientific areas covered by more than one Panel. The main objective of developing cross‐cutting guidance documents is to harmonise food and feed safety risk assessment in EFSA. The document outlines the procedures for the identification of needs for cross‐cutting guidance documents, their development, implementation, their review and revision. [ABSTRACT FROM AUTHOR]

Food contact materials are all materials and articles intended to come directly or indirectly into contact with food. Before being included in the positive European 'Union list' of authorized substances (monomers, other starting substances and additives) for plastic food contact materials, the European Food Safety Authority (EFSA) must assess their safety 'in use'. If relevant for risk, the safety of the main impurities, reaction and degradation products originating from the manufacturing process is also evaluated. Information on genotoxicity is always required irrespective of the extent of migration and the resulting human exposure, in view of the theoretical lack of threshold for genotoxic events. The 2008 EFSA approach, requiring the testing of food contact materials in three in vitro mutagenicity tests, though still acceptable, is now superseded by the 2011 EFSA Scientific Committee's recommendation for only two complementary tests including a bacterial gene mutation test and an in vitro micronucleus test, to detect two main genetic endpoints (i.e., gene mutations and chromosome aberrations). Follow-up of in vitro positive results depends on the type of genetic effect and on the substance's systemic availability. In this study, we provide an analysis of the data on genotoxicity testing gathered by EFSA on food contact materials for the period 1992-2015. We also illustrate practical examples of the approaches that EFSA took when evaluating 'non standard' food contact chemicals (e.g., polymeric additives, oligomer or other reaction mixtures, and nanosubstances). Additionally, EFSA's experience gained from using non testing methods and/or future possibilities in this area are discussed. Environ. Mol. Mutagen. 58:361-374, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Styrene is one of the most important monomers produced worldwide. IARC classified styrene as a possible carcinogen to humans (group 2B). Styrene-7,8-oxide (SO) is the main reactive metabolite of styrene, and it is found to be genotoxic in several in vitro test systems. Styrene and styrene-7,8-oxide (SO) toxicity to HepG2 cells was investigated by evaluating end-points such as heat shock proteins (Hsps), metallothioneins (MT), apoptosis-related proteins, accumulation of styrene within the cells and expression of two isoforms of cytochrome P450. The potential activity of styrene and styrene-7,8-oxide in modulating gene expression was also investigated. The results showed induction of Hsp70, metallothioneins, BclXS/L and c-myc expression and a decrease in Bax expression in HepG2 after treatments, confirming that these compounds activated protective mechanisms. Moreover, up-regulation of TGF β2 and TGF βRIII in HepG2 cells was found after exposure to styrene, while in human primary hepatocytes these genes were down-regulated after both treatments. Finally, it was found that styrene and SO treatments did not induce CYP1A2 and CYP2E1 protein expression. In conclusion, both compounds caused toxic stress in HepG2 cells, with SO being more toxic; in the meantime, a different effect of the two compounds in HepG2 cells and primary human hepatocytes was observed regarding their activity in gene modulation. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The p53 protein is an inducible transcription factor with multiple anti-proliferative roles in response to genotoxic damage; unprogrammed proliferative stimuli; and deprivation of oxygen, nutrients, or ribonucleotides. Inactivation of the TP53 gene by mutation or deletion is the most common event in human cancer. Loss of p53 function compromises genetic homeostasis in cells exposed to mutagens and prevents normal cytotoxic responses to cancer therapies. Genetic and pharmacological approaches are being developed with the ultimate goal of restoring or controlling p53 functions in cancer patients.Genetic interventions aiming at expressing wild-type TP53 in cancer cells, either by retroviral or adenoviral transfer, have met limited clinical success. However, recently, the use of a defective adenovirus (ONYX-015) that selectively kills p53-incompetent cells has shown promising effects in pre-clinical and clinical studies. Pharmacological methods are under development to either stimulate wild-type p53 protein function or induce p53 mutant proteins to resume wild-type functions. These methods are based on small chemicals (CP-31388, PRIMA-1), peptides (CDB3), or single-chain Fv antibody fragments corresponding to defined p53 domains. In addition, detection of mutant TP53 may also serve as a marker for early cancer detection, prediction, and prognosis. In this review, we discuss the mechanisms underlying these approaches and their perspectives for cancer therapy. [ABSTRACT FROM AUTHOR]

The reliability of a simple method evaluating the pattern of subcellular binding of Adriamycin (Adriamycin binding assay, ABA) as an index of sensitivity was demonstrated in different primary cultures and in sensitive and resistant cell lines of human osteosarcoma. After exposure to Adriamycin (10 μg/ml for 30 min at 37°C), living sensitive cells showed selective intranuclear uptake of the drug, whereas in resistant cells no distinct subcellular distribution was observed. The binding pattern of Adriamycin in sensitive and in highly resistant cells was inversely related to the expression of P-glycoprotein. However, low levels of resistance in vitro, not detectable by increased levels of expression of P-glycoprotein, were revealed by ABA. The use of ABA in combination with the estimate of P-glycoprotein expression is recommended in clinical practice as an accurate means for predicting the sensitivity of osteosarcoma to Adriamycin. [ABSTRACT FROM AUTHOR]

The European Food Safety Authority (EFSA) carried out a public consultation to receive input from the scientific community and all interested parties on the genotoxicity assessment of chemical mixtures. The draft statement was prepared by a dedicated working group of the Scientific Committee and endorsed by the Scientific Committee for public consultation at its 89th plenary meeting of 28‐29 May 2018. The public consultation for this document was open from 26 June until 9 September 2018. EFSA received 73 comments from 16 interested parties. EFSA's Scientific Committee wishes to thank all stakeholders for their contributions. This report presents statistics on the comments received and provides a summarised description of how the comments were addressed in the finalisation of the document. The stakeholders valuable and detailed comments were taken into account by the Scientific Committee to prepare an updated version of the statement on genotoxicity assessment of mixtures. The statement was discussed and adopted at the Scientific Committee plenary meeting on 22 November 2018, and is published in the EFSA Journal. This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2019.5519/full [ABSTRACT FROM AUTHOR]