Inhibition of intracerebral glioblastoma growth by targeting the insulin-like growth factor 1 receptor involves different context-dependent mechanisms.

Background: Signaling by insulin-like growth factor 1 receptor (IGF-1R) can contribute to the formation and progression of many diverse tumor types, including glioblastoma. We investigated the effect of the IGF-1R blocking antibody IMC-A12 on glioblastoma growth in different in vivo models.

Methods: U87 cells were chosen to establish rapidly growing, angiogenesis-dependent tumors in the brains of nude mice, and the GS-12 cell line was used to generate highly invasive tumors.

The effect of pro-inflammatory conditioning and/or high glucose on telomere shortening of aging fibroblasts.

Unlabelled: Cardiovascular disease and diabetes have been linked to shorter telomeres, but it is not yet clear which risk factors contribute to shorter telomeres in patients. Our aim was to examine whether pro-inflammatory conditioning, in combination or not with high glucose, result in a higher rate of telomere shortening during in vitro cellular ageing. Human fibroblasts from four donors were cultured for 90 days in: 1) medium lacking ascorbic acid only, 2) 10 mM buthionine sulphoximine (BSO) (pro-oxidant), 3) 25 mM D-glucose, 4) 1 ng/ml IL1B and 5) 25 mM D-glucose+1 ng/ml IL1B.

Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells.

Fluctuations in oxygen tension during tissue remodeling impose a major metabolic challenge in human tumors. Stem-like tumor cells in glioblastoma, the most common malignant brain tumor, possess extraordinary metabolic flexibility, enabling them to initiate growth even under non-permissive conditions. We identified a reciprocal metabolic switch between the pentose phosphate pathway (PPP) and glycolysis in glioblastoma stem-like (GS) cells.

Erlotinib resistance in EGFR-amplified glioblastoma cells is associated with upregulation of EGFRvIII and PI3Kp110δ.

Background: The treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors like erlotinib has not met expectations for glioblastoma therapy, even for EGFR-overexpressing tumors. We determined possible mechanisms of therapy resistance using the unique BS153 glioblastoma cell line, which has retained amplification of the egfr gene and expression of EGFR variant (v)III.

Methods: Functional effects of erlotinib, gefitinib, and cetuximab on BS153 proliferation, migration, and EGFR-dependent signal transduction were systematically compared in vitro.