Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial

Background:Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma.Methods:In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated.Results:The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log 10 CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log 10 CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated wit

TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer.

PURPOSE: To infer the prognostic value of simultaneous androgen receptor (AR) and TP53 profiling in liquid biopsies from metastatic castration-resistant prostate cancer (mCRPC) patients starting a new line of AR signalling inhibitors (ARSi). EXPERIMENTAL DESIGN: Between March 2014 and April 2017, we recruited mCRPC patients (n=168) prior to ARSi in a cohort study encompassing 10 European centres. Blood samples were collected for comprehensive profiling of CellSearch-enriched circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA). Targeted CTC RNA-seq allowed the detection of eight AR splice variants (ARVs). Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was applied to identify amplifications, loss-of-heterozygosity, mutations and structural rearrangements in ctDNA. Clinical or radiological progression-free survival (PFS) was estimated by Kaplan-Meier analysis, and independent associations were determined using multivariable Cox-regression models. RESULTS: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumour burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value (HR 1.88, 95%CI 1.18-3.00, p = 0.008), and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs 7.51 vs 2.62 months, p < 0.0001), which was validated in an independent mCRPC cohort (n=202) starting first-line ARSi (median, 14.3 vs 6.39 vs 2.23 months, p < 0.0001). CONCLUSIONS: In an all-comer cohort, tumour burden estimates and TP53 outperform any AR perturbation to infer prognosis

DECOS and NEG Basis for an Occupational Standard Glutaraldehyde

Glutaraldehyde is used, among other things, as a fixative in electron microscopy, a disinfectant for instruments and in chemical industry. It is a skin and mucous membrane irritant. Glutaraldehyde is a skin allergen and may cause respiratory allergic reactions. In rats and mice histopathological effects in the nose have been demonstrated. Glutaraldehyde is genotoxic in vitro and induces mutations in both bacterial and mammalian cells. It also produces sister chromatid exchanges and chromosomal aberrations in mammalian cells in vitro. Based on relatively few available data the critical effect when occupationally exposed is irritation of the skin, the eyes and the mucous membranes.Glutaraldehyd används bl a som fixativ i elektronmikroskopi, som desinfektionsmedel för instrument och i kemisk industri. Ämnet irriterar hud och slemhinnor. Glutaraldehyd är en hudallergen och kan ge allergiska reaktioner i andningsvägarna. Hos råtta och mus har histopatologiska effekter i nosen påvisats. Glutaraldehyd är genotoxisk in vitro och inducerar mutationer i såväl bakterier som mammalieceller. Det ger även systerkromatidutbyten och kromosomaberrationer i mammalieceller in vitro. Baserat på relativt få tillgängliga data är den kritiska effekten vid yrkesmässig exponering irritation av hud, ögon och slemhinnor

Towards an Integral View of the Technology Valorisation Process

No abstract available

Towards an Integral View of the Technology Valorisation Process

No abstract available