Preclinical evaluation of binimetinib (MEK162) delivered via polymeric nanocarriers in combination with radiation and temozolomide in glioma.

Background And Purpose: Glioblastoma multiforme (GBM) is the most aggressive subtype of malignant gliomas, with an average survival rate of 15 months after diagnosis. More than 90% of all GBMs have activating mutations in the MAPK/ERK pathway. Recently, we showed the allosteric MEK1/2 inhibitor binimetinib (MEK162) to inhibit cell proliferation and to enhance the effect of radiation in preclinical human GBM models.

Reversed phase free ion selective radiotracer extraction (RP-FISRE): a new tool to assess the dynamic stabilities of metal (-organic) complexes, for complex half-lives spanning six orders of magnitude.

This paper introduces reversed phase free ion selective radiotracer extraction (RP-FISRE) as a new tool to assess the stability of metal complexes, as illustrated by the assessment of the stability of [(177)Lu]Lu-DOTA-octreotate. To this end, the TUDelft-developed FISRE, where the released metal is column-retained and the complex eluted, was changed into RP-FISRE, where the complex is column-retained and the released metal is eluted. This change in the approach allows for studies to be performed with high stability complexes.

Phenylboronate 160Tb complexes for molecular recognition of glycoproteins expressed on tumor cells.

The over-expression of sialic acid on the surface of cancer cells compared with normal ones makes this nine-carbon sugar an attractive biomarker for molecular diagnosis and therapy. Here, we describe a study on the molecular recognition of sialic acid end groups on the surface of human glioma cells by (160)Tb-DTPA-EN(2), (160)Tb-DTPA-(ENPBA)(2) and (160)Tb-DTPA-(PBA)(2) complexes. The results show Tb-DTPA-(ENPBA)(2) to be the most efficient targeting agent, due to the electrostatic interaction between its two positively charged ammonium groups and the negatively charged cell surface, which provides an additional stabilization of the covalent binding through the PBA moieties and the sialic acid diol functions.

Optimization, application, and interpretation of lactate dehydrogenase measurements in microwell determination of cell number and toxicity.

The lactate dehydrogenase (LDH) assay was addressed for its sensitivity, disturbances by foaming, and cell number and size. Cells were from a U-251 MG grade IV human glioblastoma brain tumor cell line used in 100-microl well volumes. Cells were counted by microscopy and Coulter counting; assays were LDH or trypan blue.