We found that glioblastoma resistance to gefitinib may be mediated by an adaptive pro-survival TNFα-JNK-Axl signaling axis, and that high TNFα levels in the glioblastoma microenvironment may further intensify primary resistance.
Human mesenchymal stem cell (MSC)-based tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene delivery is regarded as an effective treatment for glioblastoma (GBM).
Treatment of human U251 and TG1 glioblastoma cells with both flavonoids also modulated negatively the expression of mRNA for IL-6 and IL-10 and positively the expression of mRNA for TNF characterizing changes to the immune regulatory profile.
In addition, by pretreating hAMSCs expression of tumor necrosis factor-related apoptosis-inducing ligand with TGF-β, we achieved significant enhancements in the therapeutic efficacy as demonstrated by an increased number of migrated hAMSCs to target sites, decreased tumor volume, and prolonged survival time in a murine model of GBM.
Mu-2-related death-inducing gene (MUDENG, <i>MuD</i>) has been reported to be involved in the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-associated apoptotic pathway of glioblastoma multiforme (GBM) cells; however, its expression level, interactors, and role in tumors are yet to be discovered.
GBM cells are frequently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and finding new combinatorial therapies to sensitize glioma cells to TRAIL remains an important challenge.
Treatment of GBM cells with MC4040 and MC4041 also impaired the GBM pro-inflammatory phenotype, with a significant decrease of TGF-β, TNF-α, and IL-6, joined to an increase of the anti-inflammatory cytokine IL-10.
We created constitutive and regulatable miR-7 expression vectors and utilized pharmacological inhibition of caspases and genetic loss of function to study the effect of forced expression of miR-7 on death receptor (DR) pathways in a cohort of GBM with established resistance to tumor necrosis factor apoptosis inducing ligand (TRAIL) and in patient-derived primary GBM stem cell (GSC) lines.
The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor types, including glioblastoma (GBM), the most common and lethal form of adult brain cancer.
Our prior work has demonstrated an important role for the tumor necrosis factor-like weak inducer of apoptosis (TWEAK) receptor fibroblast growth factor-inducible 14 (Fn14) in GBM pathobiology.
Peripheral blood from 205 treatment-naïve patients with glioma (GBM = 145; non-GBM = 60) was obtained on the day of surgery to measure (i) circulating T-cells reacting to viral antigens and TAAs, in the presence or absence of cytokine conditioning with IL-2/IL-15/IL-21 or IL-2/IL-7, and (ii) serum cytokine levels (IL-4, IL-5, IL-6, TNF-α, IFN-γ and IL-17A).
Furthermore, our data identified MAPK-ERK-YAP signaling pathways as the primary molecular mechanisms by which TNFα modulated mitochondrial fission and glioblastoma apoptosis.
We identified that CD44, ATP binding cassette subfamily C member 3 (ABCC3), and tumor necrosis factor receptor subfamily member 1A (TNFRSF1A) as highly expressed genes in GBMs are associated with patients' poor outcomes and therapy resistance.
Our findings provide a possible explanation for the failures of anti-EGFR therapy in GBM and suggest a new approach to the treatment of EGFR-expressing GBM using a combination of EGFR and TNF inhibition.
Serial imaging showed that h-iNSC<sup>TE</sup> delivery of the proapoptotic agent tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) reduced the size of solid human GBM xenografts 250-fold in 3 weeks and prolonged median survival from 22 to 49 days.
Inhibition of NF-κB Pathway and Modulation of MAPK Signaling Pathways in Glioblastoma and Implications for Lovastatin and Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) Combination Therapy.
Activation of NF-κB by TNFα decreases calcium induced mPTP opening, elevates mitochondrial potential and increases reactive oxygen species (ROS) production in both T98G human glioblastoma cells and rat cortical neurons.
We recently reported that mammalian target of rapamycin inhibitors-rapamycin, temsirolimus, torin 1, and PP242-suppressed invasion and migration promoted by tumor necrosis factor-alpha and phorbol-myristate-acetate in glioblastoma cells.
In in vitro study, HCMV infection induced the expression of interleukin 6 and tumor necrosis factor-α in human glioblastoma U87 MG (U87) cells and human umbilical vein endothelial cells (HUVECs).
The highest mean values of PHLPP1 mRNA and protein were found in non-glioma brain tissues whereas the lowest mean values were found in those in glioblastoma with an increase of TNF-α, IL-17, IL-1β (p<0.05).
These observations demonstrate that olive oil compounds inhibit the effect of the chronic inflammatory microenvironment on glioblastoma progression through TNF-α actions and may be useful in cancer chemoprevention.
Glioblastoma microenvironment contains high levels of TNFα and IL-1β, which mediate inflammation through induction of a local network of cytokines and chemokines.