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Glioblastoma multiforme is the most common and deadliest form of brain cancer. Glioblastomas are infiltrated by a high number of microglia, which promote tumor growth and surrounding tissue invasion. However, it is unclear how microglia and glioma cells physically interact and if there are differences, depending on glioma cell type. Hence, we have developed a novel live imaging assay to study microglia–glioma interactions in vivo in the zebrafish brain. We transplanted well-established human glioblastoma cell lines, U87 and U251, into transgenic zebrafish lines with labelled macrophages/microglia. Our confocal live imaging results show distinct interactions between microglia and U87, as well as U251 glioblastoma cells that differ in number and nature. Importantly these interactions do not appear to be antitumoral as zebrafish microglia do not engulf and phagocytose the human glioblastoma cells. Finally, xenotransplants into the irf8−/− zebrafish mutant that lacks microglia, as well as pharmacological inhibition of the CSF-1 receptor (CSF-1R) on microglia, confirm a prominent role for zebrafish microglia in promoting human glioblastoma cell growth. This new model will be an important tool for drug screening and the development of future immunotherapeutics targeting microglia within glioma.

We consider the enzyme kinetic reaction scheme originally proposed by V. HenriВ  of single enzyme-substrate dynamics where two fractions of the enzyme - free and bound - are involved. Henri's scheme involves four concentrations and three rate constants and via the mass action law it is translated into a systemВ  of four ODE's. On two case studies we demonstrate how the rate constants can be computed whenever time course experimental data are available. The obtained results are compared with analogous results implied by classical Michaelis-Menten model. Our approach focuses on the uncertainties in the experimental data, as well as on the use of contemporary computational tools such as CAS Mathematica.

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