Hoogveen en klimaatverandering in Nederland

Voor de instandhouding en ontwikkeling van hoogveen zijn het neerslagoverschot, de temperatuur en de positie in het landschap belangrijk. Gunstige ontwikkelingen doen zich voor in gebieden waar het (actieve) hoogveen water uit zijn omgeving ontvangt. De landelijke instandhoudingsdoelen voor Natura 2000-habitattype Actieve hoogvenen kunnen waarschijnlijk ook onder het klimaatscenario W+ worden gerealiseerd: behoud van kwaliteit en oppervlakte zijn kansrijk en verbetering van kwaliteit en uitbreiding van oppervlakte zijn mogelijk. Voorwaarden hierbij zijn een optimale waterhuishouding. Dat wil zeggen voldoende hoge grondwaterstanden in de zandondergrond en de veenbasis in combinatie met een waterondoorlatende (veen)laag en/of de toevoer van lokaal grondwater. Om hoogvenen op de lange termijn in Nederland te behouden onder het W+- scenario zijn waterhuishoudkundige maatregelen nodig, zoals de aanleg en inrichting van bufferzones en compartimenten en/of door het bevorderen van kwel

Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches

Mogelijkheden voor herstelbeheer in hellingbossen op kalkrijke bodem in Zuid-Limburg : resultaten eerste onderzoekfase

Het doel van het OBN-onderzoek naar de Zuid-Limburgse hellingbossen is het aangeven van concrete opties voor de beheerder waarmee de oorspronkelijke diversiteit aan planten- en diersoorten van deze bossen behouden dan wel hersteld kan worden. Uitgangspunt hierbij is dat er sprake moet zijn van een gedifferentieerd beheer, waarbij rekening wordt gehouden met de – grotendeels geologisch bepaalde – landschappelijke context, waarbij niet alleen verschillende regio’s (löss-, mergel en vuursteengebied) maar binnen elke regio ook verschillende hellingzones met hun specifieke waarden worden onderscheide

Preclinical assessment of ADAM9-responsive mesoporous silica nanoparticles for the treatment of pancreatic cancer

Supramolecular & Biomaterials Chemistr

ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit

Ccaat/enhancer-binding protein delta (C/ebpδ): A previously unrecognized tumor suppressor that limits the oncogenic potential of pancreatic ductal adenocarcinoma cells

CCAAT/enhancer-binding protein δ (C/EBPδ) is a transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in pancreatic cancer. We determined C/EBPδ expression in biopsies from pancreatic cancer patients using public gene-expression datasets and in-house tissue microarrays. We found that C/EBPδ is highly expressed in healthy pancreatic ductal cells but lost in pancreatic ductal adenocarcinoma. Furthermore, loss of C/EBPδ correlated with increased lymph node involvement and shorter overall survival in pancreatic ductal adenocarcinoma patients. In accordance with this, in vitro experiments showed reduced clonogenic capacity and proliferation of pancreatic ductal adenocarcinoma cells following C/EBPδ re-expression, concurrent with decreased sphere formation capacity in soft agar assays. We thus report a previously unrecognized but important tumor suppressor role of C/EBPδ in pancreatic ductal adenocarcinoma. This is of particular interest since only few tumor suppressors have been identified in the context of pancreatic cancer. Moreover, our findings suggest that restoration of C/EBPδ activity could hold therapeutic value in pancreatic ductal adenocarcinoma, although the latter claim needs to be substantiated in future studies

A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas

Targeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic biomarkers in resectable EAC treated with curative intent. The Medline, Cochrane and EMBASE databases were systematically searched, focusing on overall survival (OS). The quality of the studies was assessed using a scoring system ranging from 0–7 points based on modified REMARK criteria. To evaluate all identified prognostic biomarkers, the hallmarks of cancer were adapted to fit all biomarkers based on their biological function in EAC, resulting in the features angiogenesis, cell adhesion and extra-cellular matrix remodeling, cell cycle, immune, invasion and metastasis, proliferation, and self-renewal. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were derived by random effects meta-analyses performed on each hallmarks of cancer feature. Of the 3298 unique articles identified, 84 were included, with a mean quality of 5.9 points (range 3.5–7). The hallmarks of cancer feature ‘immune’ was most significantly associated with worse OS (HR 1.88, (95%CI 1.20–2.93)). Of the 82 unique prognostic biomarkers identified, meta-analyses showed prominent biomarkers, including COX-2, PAK-1, p14ARF, PD-L1, MET, LC3B, IGFBP7 and LGR5, associated to each hallmark of cancer