MSI as a predictive factor for treatment outcome of gastroesophageal adenocarcinoma.

Gastroesophageal cancers are a major cause of death worldwide and treatment outcomes remain poor. Adequate predictive biomarkers have not been identified. Microsatellite instability (MSI) as a result of mismatch repair deficiency is present in four to twenty percent of gastroesophageal cancers and has been associated with favorable survival outcomes compared to microsatellite stable tumors. This prognostic advantage may be related to immunosurveillance, which may also explain the favorable response to immune checkpoint inhibition observed in MSI high (MSI-H) tumors. The value of conventional cytotoxic treatment in MSI-H tumors is unclear and results on its efficacy range from detrimental to beneficial effects. Here the recent data on MSI as a predictive factor for outcome of gastroesophageal cancer treatment is reviewed.

The PFOA substitute GenX detected in the environment near a fluoropolymer manufacturing plant in the Netherlands.

The ban on perfluorooctanoic acid (PFOA) has led to the production and use of alternative fluorinated compounds such as GenX. Limited information is available on the occurrence of this PFOA substitute. In this pilot study, we investigated the presence of GenX in/on grass and leaf samples collected near a fluoropolymer manufacturing plant in the Netherlands and in drinking water produced from surface and surface-water influenced groundwater intake points within 25 km from the plant. GenX was detected in/on all grass and leaf samples collected within 3 km north-east from the plant, with levels ranging from 1 to 27 ng/g wet weight (ww) and 4.3-86 ng/g ww, respectively. The PFOA levels in/on grass and leaves were lower, ranging from 0.7 to 11 ng/g ww and 0.9-28 ng/g ww, respectively. A declining concentration gradient of GenX and PFOA with increasing distance from the plant was observed, which suggests that the plant is a point source of GenX and was a point source for PFOA in the past. In all drinking water samples, GenX and PFOA were detected with levels ranging from 1.4 to 8.0 ng/L and 1.9-7.1 ng/L, respectively. The detection of GenX, which is only used since 2012, in/on grass and leaves and in drinking water indicates that GenX is now distributed through the environment. The presence of GenX and PFOA in/on grass and leaves within 3 km north-east of the plant also suggests that these chemicals could also be present on the locally grown food in gardens around the factory.

Microplastics en route: Field measurements in the Dutch river delta and Amsterdam canals, wastewater treatment plants, North Sea sediments and biota.

Environmental contamination by plastic particles, also known as 'microplastics', brings synthetic materials that are non-degradable and biologically incompatible into contact with ecosystems. In this paper we present concentration data for this emerging contaminant in wastewater treatment plants (WWTPs) and freshwater and marine systems, reflecting the routes via which these particles can travel and the ecosystems they potentially impact along their path. Raw sewage influents, effluents and sewage sludge from seven municipal WWTPs in the Netherlands contained mean particle concentrations of 68-910L-1, 51-81L-1 and 510-760kg-1 wet weight (ww), respectively (particle sizes between 10 and 5000µm). Even after treatment, wastewater constitutes a source of microplastic pollution of surface waters, and via biosolids applications in farming and forestry, plastic retained in sewage sludge can be transferred to terrestrial environments. The WWTPs investigated here had a mean microplastics retention efficiency of 72% (s.d. 61%) in the sewage sludge. In the receiving waters of treated and untreated wastewaters, we detected high microplastic levels in riverine suspended particulate matter (1400-4900kg-1 dry weight (dw)) from the Rhine and Meuse rivers. Amsterdam canal water sampled at different urban locations contained microplastic concentrations (48-187L-1), similar to those observed in wastewater that is emitted from sewage treatment facilities in the area. At least partial settling of the particles occurs in freshwater as well, as indicated by microplastics in urban canal sediments (<68 to 10,500particleskg-1dw). Microplastics in suspension in the water column have the potential to be discharged into the sea with other riverine suspended particulates. We report microplastic concentrations from 100 up to 3600particleskg-1 dry sediment collected at 15 locations along the Dutch North Sea coast. The high microplastic enrichment in marine sediments compared to most literature data for seawater at the surface supports the hypothesis of a seabed sink for these materials. Marine species are heavily exposed to plastic particles. Body residues between 10 and 100particlesg-1dw were measured in benthic macroinvertebrate species inhabiting the Dutch North Sea coast: filter-feeding mussels and oysters (species for human consumption) as well as other consumers in the marine food chain.

Exposure to organophosphate and polybrominated diphenyl ether flame retardants via indoor dust and childhood asthma.

Although the ubiquitous detection of polybrominated diphenyl ether (PBDE) and organophosphate flame retardants (PFRs) in indoor dust has raised health concerns, only very few epidemiological studies have assessed their impact on human health. Inhalation of dust is one of the exposure routes of FRs, especially in children and can be hazardous for the respiratory health. Moreover, PFRs are structurally similar to organophosphate pesticides, which have been associated with allergic asthma. Thus, we investigated whether the concentrations of PFRs and PBDEs in indoor dust are associated with the development of childhood asthma. We selected 110 children who developed asthma at 4 or at 8 years old and 110 matched controls from a large prospective birth cohort (BAMSE - Barn, Allergy, Milieu Stockholm Epidemiology). We analyzed the concentrations of 7 PFRs and 21 PBDEs in dust collected around 2 months after birth from the mother's mattress. The abundance rank in dust was as follows: TBOEP⪢TPHP>mmp-TMPP>EHDPHP~TDCIPP>TCEP~TCIPP~BDE-209⪢BDE-99>BDE-47>BDE-153>BDE-183>BDE-100. There was no positive association between the FRs in mattress dust and the development of childhood asthma. In contrast, dust collected from mattresses of the mothers of children who would develop asthma contained significant lower levels of TPHP and mmp-TMPP. This study provides data on a wide range of PFRs and PBDEs in dust samples and development of asthma in children.

Halogenated contaminants in farmed salmon, trout, tilapia, pangasius, and shrimp.

Polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and dibenzo-p-furans (PCDD/Fs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane diastereomers (HBCDs), and perfluorinated compounds (PFCs) were analyzed in popular farmed fish such as salmon, trout, tilapia, and pangasius and in farmed shrimp. The samples originated from southeast Asia, Europe, and South America. Results show the following: (i) Carnivorous species contained higher contaminant concentrations than omnivorous species. (ii) Contaminant concentrations generally decreased per species in the following order of salmon > trout >> tilapia approximately equal to pangasius approximately equal to shrimp. (iii) Most contaminant concentrations decreased in the following order of PCBs approximately equal to dichloro-diphenyl-trichloroethanes (DDTs) >> hexachlorobenzene approximately equal to pentachlorobenzene approximately equal to dieldrin approximately equal to PBDEs approximately equal to alpha-HBCD approximately equal to perfluorooctane sulfonate (PFOS) >> World Health Organization toxic equivalents (WHO-TEQ) [PCDD/Fs and dioxin-like (dl)-PCBs]. (iv) Contaminant concentrations were very low (mostly <1 ng/g wet weight) and far below the European and Dutch legislative limits. (v) Contaminant concentrations in farmed shrimp, pangasius, and tilapia were lower than those in wild fish, whereas contaminant concentrations in farmed salmon and trout were higher than those in lean wild marine fish. From the five species investigated, salmon is predominantly responsible (97%) for human exposure to the sum of the investigated contaminants. The contribution of trout, tilapia, pangasius, and shrimp is small (3%) because contaminant concentrations and consumption volumes were much lower.

Metallothionein-bound cadmium in the gut of the insect Orchesella cincta (Collembola) in relation to dietary cadmium exposure.

Metallothionein is considered to be a potential biomarker for heavy metal exposure in the terrestrial environment. However, limited information is available on metallothioneins from insects, a major class of terrestrial invertebrates. In this study we have quantified metallothioneins in the springtail Orchesella cincta by determining metallothionein-bound cadmium after separation of these proteins using gel filtration and reversed phase chromatography from total body homogenates of animals dietary exposed to different concentrations of cadmium. Furthermore, we have studied in more detail where cadmium and metallothionein-bound cadmium is located within this animal. The concentration of metallothionein-bound cadmium increases with the exposure concentration in the same way as the total internal concentration. Both reach a plateau at an exposure concentration of approximately 1.0 micromol Cd/dry food. Cadmium is primarily located within the gut of O. cincta and isolation of metallothionein from this organ gives results identical to isolations from total bodies. Based on this results an estimation of the metallothionein level at the highest exposure concentration results in a concentration of about 115 microg metallothionein/g fresh gut. The O. cincta metallothionein gives the possibility of using this protein as a biomarker for heavy metal exposure in soil insects.

Primary structure of a cadmium-induced metallothionein from the insect Orchesella cincta (Collembola).

The induction of metallothionein was studied in the springtail Orchesella cincta (Collembola), a species of insect living in forest soils. Upon dietary exposure to Cd, two Cd-binding, cysteine-rich peptides were isolated from whole-body homogenates, using gel filtration and reversed-phase FPLC. Mass spectrometric analysis revealed that the molecular masses of these peptides were 2989 Da and 4139 Da, respectively. Amino acid sequencing of the 2989-Da peptide resulted in a sequence typical for a metallothionein. Sequencing of the 4139-Da protein was unsuccessful, probably due to N-terminal blockage. Using different PCR techniques (3' and 5' RACE) with (degenerate) primers based on the identified amino acid sequence of the 2989 Da peptide, a metallothionein cDNA was isolated. The sequence of this cDNA potentially codes for a protein of 77 amino acids. The 2989 Da peptide corresponds to the C-terminal part of this protein. The 4139-Da protein is probably encoded by the N-terminal part of this protein. These results suggest that the identified peptides are products of one gene, and that the primary gene product is subject to post-translational processing. The deduced amino acid sequence of the O. cincta metallothionein shows low sequence similarity with metallothioneins from Drosophila. The similarity between O. cincta MT and MTs of invertebrates is not higher than that between O. cincta and vertebrates.