Relevance of neurotrophin receptors CD271 and TrkC for prognosis, migration, and proliferation in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and often has a poor prognosis. The present study investigated the role of the low affinity nerve growth factor receptor CD271 as a putative therapy target in HNSCC. Neurotrophins that bind to CD271 also have a high affinity for the tropomyosin receptor kinase family (Trk), consisting of TrkA, TrkB, and TrkC, which must also be considered in addition to CD271. A retrospective study and functional in vitro cell line tests (migration assay and cell sorting) were conducted in order to evaluate the relevance of CD271 expression alone and with regard to Trk expression. CD271 and Trks were heterogeneously expressed in human HNSCC. The vast majority of tumors exhibited CD271 and TrkA, whereas only half of the tumors expressed TrkB and TrkC. High expression of CD271-positive cells predicted a bad clinical outcome of patients with HNSCC and was associated with distant metastases. However, the human carcinomas that also expressed TrkC had a reduced correlation with distant metastases and better survival rates. In vitro, CD271 expression marked a subpopulation with higher proliferation rates, but proliferation was lower in tumor cells that co-expressed CD271 and TrkC. The CD271 inhibitor LM11A 31 suppressed cell motility in vitro. However, neither TrkA nor TrkB expression were linked to prognosis or cell proliferation. We conclude that CD271 is a promising candidate that provides prognostic information for HNSCC and could be a putative target for HNSCC treatment

Simultaneous Quantification and Pharmacokinetic Characterization of Doxapram and 2-Ketodoxapram in Porcine Plasma and Brain Tissue

Atrial fibrillation (AF) is an arrhythmia associated with an increased stroke risk and mortality rate. Current treatment options leave unmet needs in AF therapy. Recently, doxapram has been introduced as a possible new option for AF treatment in a porcine animal model. To better understand its pharmacokinetics, three German Landrace pigs were treated with intravenous doxapram (1 mg/kg). Plasma and brain tissue samples were collected. For the analysis of these samples, an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the simultaneous measurement of doxapram and its active metabolite 2-ketodoxapram was developed and validated. The assay had a lower limit of quantification (LLOQ) of 10 pg/mL for plasma and 1 pg/sample for brain tissue. In pigs, doxapram pharmacokinetics were biphasic with a terminal elimination half-life (t1/2) of 1.38 ± 0.22 h and a maximal plasma concentration (cmax) of 1780 ± 275 ng/mL. Its active metabolite 2-ketodoxapram had a t1/2 of 2.42 ± 0.04 h and cmax of 32.3 ± 5.5 h after administration of doxapram. Protein binding was 95.5 ± 0.9% for doxapram and 98.4 ± 0.3% for 2-ketodoxapram with a brain-to-plasma ratio of 0.58 ± 0.24 for doxapram and 0.12 ± 0.02 for 2-ketodoxapram. In conclusion, the developed assay was successfully applied to the creation of pharmacokinetic data for doxapram, possibly improving the safety of its usage

Hybrid molecular graphene transistor as an operando and optoelectronic platform

International audienceLack of reproducibility hampers molecular devices integration into large-scale circuits. Thus, incorporating operando characterization can facilitate the understanding of multiple features producing disparities in different devices. In this work, we report the realization of hybrid molecular graphene field effect transistors (m-GFETs) based on 11-(Ferrocenyl)undecanethiol (FcC 11 SH) micro self-assembled monolayers (μSAMs) and high-quality graphene (Gr) in a back-gated configuration. On the one hand, Gr enables redox electron transfer, avoids molecular degradation and permits operando spectroscopy. On the other hand, molecular electrode decoration shifts the Gr Dirac point (V DP ) to neutrality and generates a photocurrent in the Gr electron conduction regime. Benefitting from this heterogeneous response, the m-GFETs can implement optoelectronic AND/OR logic functions. Our approach represents a step forward in the field of molecular scale electronics with implications in sensing and computing based on sustainable chemicals