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On the analysis of a mathematical model of CAR-T cell therapy for glioblastoma: Insights from a mathematical model

Bodnar Marek, Foryś Urszula, Piotrowska Monika J., Bodzioch Mariusz, Romero-Rosales Jose A., Belmonte-Beitia Juan

International Journal of Applied Mathematics and Computer Science

2023

Vol. 33, no. 3

379--394

Chimeric antigen receptor T (CAR-T) cell therapy has been proven to be successful against different leukaemias and lymphomas. Its success has led, in recent years, to its use being tested for different solid tumours, including glioblastoma, a type of primary brain tumour, characterised by aggressiveness and recurrence. This paper presents an analytical study of a mathematical model describing the competition of CAR-T and glioblastoma tumour cells, taking into account their immunosuppressive capacity. The model is formulated in a general way, and its basic properties are investigated. However, most of the analysis considers the model with exponential tumour growth, assuming this growth type for simplicity. The existence and stability of steady states are studied, and the subsequent focus is on two different types of treatment: constant and periodic. Finally, protocols for CAR-T cell therapy of glioblastoma are numerically derived; these are aimed at preventing the tumour from reaching a critical size and at prolonging the patients’ survival time as much as possible. The analytical and numerical results provide theoretical support for the treatment of glioblastoma using CAR-T cells.

Protein-protein interaction and coarse grained simulation study of glioblastoma multiforme reveals novel pathways of Gpr17

Gnanavel M., Yli-Harja O., Kandhavelu M.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

2014

Vol. 18, No 4

321--325

Studies of receptor mediated signaling networks in neuronal cells pro vide a unique opportunity to uncover the basis of many diseases. Receptor signaling c ascades proceed from the cell surface, where extra cellular factors interact with their specific receptors e.g. G-Protein Coupled Receptors ( GPR ). Recent studies have shown that the activation or suppression of GPR 17 in diseased neuronal cells has potential impact in altering the tumor con ditions. We identified many hundred times expressions of GPR 17 in Glioblastoma Multiforme ( GBM ) from the RNA -Seq data. We also observed many other genes having similar expression patt erns with GPR 17, indicating possible connections of this receptor with diverse gen e products. We performed a coarse-grained simulation of ∼ 500 proteins inside a cytoplasm like a box with solvent water molecules. The summarized protein interaction networks r esulted from a coarsegrained simulation and large scale protein-protein docking reveals nov el molecular connections and pathways.