A phase I first-in-human pharmacokinetic and pharmacodynamic study of serdemetan in patients with advanced solid tumors.

Purpose: Originally isolated on the basis of its ability to induce p53, serdemetan showed potent activity in various preclinical models, inducing S-phase arrest and apoptosis in TP53 wild-type and mutant tumors. This study evaluated the safety and tolerability of serdemetan, determined the pharmacokinetic and pharmacodynamic profiles, and identified a recommended phase II dose.

Patients And Methods: Patients (71) with refractory solid tumors were allocated to dose-escalating cohorts (3+3 patients each) and received oral serdemetan once daily in 21-day cycles to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT).

Phase I and pharmacological study of the broad-spectrum tyrosine kinase inhibitor JNJ-26483327 in patients with advanced solid tumours.

Background: JNJ-26483327 is an oral, potent, multi-targeted tyrosine kinase inhibitor, inhibiting kinases of epidermal growth factor receptor (EGFR)-1, -2 and -4, rearranged during transfection (RET) receptor, vascular endothelial growth factor receptor (VEGFR)-3 and Src family (Lyn, Fyn, Yes) at low nanomolar concentrations. This phase I, accelerated titration study assessed maximum tolerated dose, safety, pharmacokinetics and pharmacodynamic effects of JNJ-26483327.

Methods: Nineteen patients with advanced cancers received JNJ-26483327 continuous twice daily (BID) in escalating dose cohorts ranging from 100 to 2100 mg.

Structural priming of adjective-noun structures in hearing and deaf children.

We examined priming of adjective-noun structures in Dutch hearing and deaf children. In three experiments, hearing 7- and 8-year-olds, hearing 11- and 12-year-olds, and deaf 11- and 12-year-olds read a prenominal structure (e.g.

Evaluative expression in deaf children's written narratives.

Background: Deaf children vary in the use of and proficiency in signed language. The majority of studies on writing skills of children who are deaf did not assess deaf children's proficiency in signed language and/or grouped together deaf children with varying sign language skills.

Aims: Adopting a bimodal bilingual perspective, we examined evaluative expression, an important narrative tool in both oral/written languages and signed languages, in narratives written in Dutch by deaf children who are proficient in Sign Language of the Netherlands (SLN) and deaf children who are low-proficient in SLN, and hearing monolingual and bilingual children.

Pharmacokinetic-pharmacodynamic modelling of fluvoxamine 5-HT transporter occupancy in rat frontal cortex.

Background And Purpose: The pharmacokinetic-pharmacodynamic (PK-PD) correlation of fluvoxamine 5-HT transporter (SERT) occupancy was determined in rat frontal cortex ex vivo.

Experimental Approach: Rats (n=47) with permanent arterial and venous cannulas received a 30 min intravenous infusion of fluvoxamine (1 or 7.3 mg kg(-1)).