Phase 1 study of the MDM2 inhibitor AMG 232 in patients with advanced P53 wild-type solid tumors or multiple myeloma

_Background_ This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). _Methods_ In the dose escalation (n = 39), patients with P53WT refractory solid tumors enrolled to receive once-dailyAMG 232 (15, 30, 60, 120, 240, 480, and 960 mg) for seven days every 3 weeks (Q3W). In the dose expansion (n = 68), patients with MDM2-amplified (well-differentiated and dedifferentiated liposarcomas [WDLPS and DDLPS], glioblastoma multiforme [GBM], or other solid tumors [OST]), MDM2-overexpressing ER+ breast cancer (BC), or MM received AMG 232 at the maximum tolerated dose (MTD). Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed. _Results_ AMG 232 had acceptable safety up to up to 240 mg

Rhizodeposition and the enhanced mineralization of 2,4-dichlorophenoxyacetic acid in soil from the Trifolium pratense rhizosphere

Enhanced biodegradation of organic xenobiotic compounds in the rhizosphere is frequently recorded although the specific mechanisms are poorly understood. We have shown that the mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) is enhanced in soil collected from the rhizosphere of Trifolium pratense[e.g. maximum mineralization rate=7.9 days-1 and time at maximum rate (t1)=16.7 days for 12-day-old T. pratense soil in comparison with 4.7 days-1 and 25.4 days, respectively, for non-planted controls). The purpose of this study was to gain a better understanding of the plant-microbe interactions involved in rhizosphere-enhanced biodegradation by narrowing down the identity of the T. pratense rhizodeposit responsible for stimulating the microbial mineralization of 2,4-D. Specifically, we investigated the distribution of the stimulatory component(s) among rhizodeposit fractions (exudates or root debris) and the influence of soil properties and plant species on its production. Production of the stimulatory rhizodeposit was dependent on soil pH (e.g. t1 for roots grown at pH 6.5 was significantly lower than for those grown at pH 4.4) but independent of soil inorganic N concentration. Most strikingly, the stimulatory rhizodeposit was only produced by T. pratense grown in non-sterile soil and was present in both exudates and root debris. Comparison of the effect of root debris from plant species (three each) from the classes monocotyledon, dicotyledon (non-legume) and dicotyledon (legume) revealed that legumes had by far the greatest positive impact on 2,4-D mineralization kinetics. We discuss the significance of these findings with respect to legume-rhizobia interactions in the rhizosphere

Rizoremediação de pentaclorofenol em um solo argiloso por sphingomonas chlorophenolica ATCC 39723 Pentachlorophenol rhizoremediation in a loamy soil by sphingomonas chlorophenolica ATCC 39723

O principal objetivo deste trabalho foi estudar a degradação de PCP por Sphingomonas chlorophenolicaem solo argiloso na presença e ausência de trigo. As concentrações de PCP foram determinadas através de Análises de Alta Performance de Cromatografia Líquida. Os efeitos tóxicos de PCP foram estudados através do monitoramento do crescimento das plantas. A biodegradação de PCP por S. chlorophenolica foi acompanhada por testes de bioluminescência de Escherichia coli HB101 pUCD607 e contagens bacterianas no solo e nas raízes. A degradação de PCP ocorreu de forma mais rápida no solo plantado e inoculado quando comparada ao solo sem plantas. Houve um aumento significativo nas populações dos organismos testados nas raízes quando comparadas com as populações presentes no solo. O monitoramento do crescimento da planta mostrou o papel protetor exercido pela S.chlorophenolica contra a toxicidade do PCP.<br>The main objective of this study was study the PCP degradation by Sphingomonas chlorophenolica in a loamy soil in the presence and absence of plants (Winter wheat). Measurements of PCP concentrations were carried out in a laboratory basis using High performance liquid chromatography analysis (HPLC). The toxic effect of PCP on plants was studied through the monitoring of the plant growth. The biodegradation of PCP by S. chlorophenolica in soil was assessed with a bioluminescence assay of Escherichia coli HB101 pUCD607 and bacterial analyses in roots and soil. The planted and inoculated soil showed a faster degradation when compared to the inoculated soil without plants. There was a significative increase in the populations of the organisms tested in the roots when compared to the soil. The monitoring of the plant growth showed a protective role of S. chlorophenolica against the toxicity of PCP in the loamy soil