Mouse DRG Cell Line with Properties of Nociceptors

In vitro cell lines from DRG neurons aid drug discovery because they can be used for early stage, high-throughput screens for drugs targeting pain pathways, with minimal dependence on animals. We have established a conditionally immortal DRG cell line from the Immortomouse. Using immunocytochemistry, RT-PCR and calcium microfluorimetry, we demonstrate that the cell line MED17.11 expresses markers of cells committed to the sensory neuron lineage. Within a few hours under differentiating conditions, MED17.11 cells extend processes and following seven days of differentiation, express markers of more mature DRG neurons, such as NaV1.7 and Piezo2. However, at least at this time-point, the nociceptive marker NaV1.8 is not expressed, but the cells respond to compounds known to excite nociceptors, including the TRPV1 agonist capsaicin, the purinergic receptor agonist ATP and the voltage gated sodium channel agonist, veratridine. Robust calcium transients are observed in the presence of the inflammatory mediators bradykinin, histamine and norepinephrine. MED17.11 cells have the potential to replace or reduce the use of primary DRG culture in sensory, pain and developmental research by providing a simple model to study acute nociception, neurite outgrowth and the developmental specification of DRG neurons

Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology

Patient-based cancer models are essential tools for studying tumor biology and for the assessment of drug responses in a translational context. We report the establishment a large cohort of unique organoids and patient-derived orthotopic xenografts (PDOX) of various glioma subtypes, including gliomas with mutations in IDH1, and paired longitudinal PDOX from primary and recurrent tumors of the same patient. We show that glioma PDOXs enable long-term propagation of patient tumors and represent clinically relevant patient avatars that retain histopathological, genetic, epigenetic, and transcriptomic features of parental tumors. We find no evidence of mouse-specific clonal evolution in glioma PDOXs. Our cohort captures individual molecular genotypes for precision medicine including mutations in IDH1, ATRX, TP53, MDM2/4, amplification of EGFR, PDGFRA, MET, CDK4/6, MDM2/4, and deletion of CDKN2A/B, PTCH, and PTEN. Matched longitudinal PDOX recapitulate the limited genetic evolution of gliomas observed in patients following treatment. At the histological level, we observe increased vascularization in the rat host as compared to mice. PDOX-derived standardized glioma organoids are amenable to high-throughput drug screens that can be validated in mice. We show clinically relevant responses to temozolomide (TMZ) and to targeted treatments, such as EGFR and CDK4/6 inhibitors in (epi)genetically defined subgroups, according to MGMT promoter and EGFR/CDK status, respectively. Dianhydrogalactitol (VAL-083), a promising bifunctional alkylating agent in the current clinical trial, displayed high therapeutic efficacy, and was able to overcome TMZ resistance in glioblastoma. Our work underscores the clinical relevance of glioma organoids and PDOX models for translational research and personalized treatment studies and represents a unique publicly available resource for precision oncology

Etude de la nutrition minérale du cotonnier -Gossypium hirsutum L.- par la méthode des variantes systématiques

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Online-on-the-spot zoeken verhoogt het gebruik van EBM tijdens consultaties

Online-on-the -spot of kortweg OOS is het zoeken op internet in een aantal EBM-databanken naar een antwoord op de vraag in aanwezigheid van de patiënt tijdens de consultatie. Methode: Wij ontwikkelden OOS als een kwaliteitsverbeteringsproject in onze huisartsengroepspraktijk. Hierbij werd eerst gezocht in de NHG standaarden en indien nodig verder in Clinical Evidence, de TRIP-database of de BMJ. Resultaten: Drie huisartsen en twee HAIO's registreerden in drie maanden tijd 365 zoekopdrachten (OOS'en) op 2920 art-patiëtncontacten, tijdens de consultatie. Dit betekende één OOS per acht patiëtncontacten. De gemiddelde duur van opzoeken en verwerken voor de patiëtn bedroeg zeven minuten. Op het einde van het OOS-project was het aantal zoekopdrachten die minder dan vijf minuten duurden, significant hooger dan bij het begin: respectievelijk 51% tegenover 33%. In acht op de tien zoekopdrachten vonden wij een antwoord, wat bij vier op de tien nieuwe informatie opleverde en bij twee op de tien tot een verandering van de medische beslissing leidde. Bij vijf op de tien OOS'en werd de patiënt direct betrokken. Besluit: OOS vormt een antwoord op de educatieve behoefte van de arts. OOS brengt patiënt, arts en bestaande wetenschappelijke evidentie samen.status: publishe