Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive death ligand in targeted cancer therapy. Many cancer cells are refractory to TRAIL-induced cell death and the mechanisms underlying resistance are unclear. The molecular mechanisms of HCC and gastric cancer cells resistant to TRAIL-induced apoptosis were explored using molecular biological and immunological methods...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are r...

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a recently identified member of the tumor necrosis factor cytokine superfamily. TRAIL has been shown to induce apoptosis in various tumor cell lines, whereas most primary cells seem to be resistant. These observations have raised considerable interest in the use of TRAIL in tumor therapy. Yet little is known about the physiologi...

Skeletal complications represent major clinical problems in multiple myeloma (MM). MM cells are known to induce differentiation of osteoclasts and inhibit osteoblasts. Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) are key molecules for osteoclastogenesis. Although OPG interacts with tumor necrosis factor-related ...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells. However, its short half-life, poor delivery, and TRAIL-resistant tumor cells have diminished its clinical efficacy. In this study, we explored whether novel delivery methods will represent new and effective ways to treat gliomas and if adjuvant therapy with the chemotherapeutic agent temozolomide woul...

TRAIL [TNF (tumour necrosis factor)-related apoptosis-inducing ligand] is a promising agent for clinical use since it kills a wide range of tumour cells without affecting normal cells. We provide evidence that pretreatment with etoposide significantly enhanced TRAIL-mediated apoptosis via up-regulation of DR5 (death receptor 5 or TRAIL-R2) expression in the caspase 8 expressing neuroblastoma ce...

Remodeling of the uterine spiral arteries during pregnancy transforms them from high to low resistance vessels that lack vasoconstrictive properties. This process is essential to meet the demand for increased blood flow imposed by the growing fetus. Loss of endothelial and smooth muscle cells (SMC) is evident in remodeled arteries but the mechanisms underlying this transformation remain unknown...

BACKGROUND TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, is a recently identified cytokine that preferentially kills transformed cells while sparing most normal cells. METHODS We investigated the ability of TRAIL alone and TRAIL in combination with cytotoxic drugs to induce apoptosis in six ovarian cancer cell lines. To get some insight into the resistance to TRAIL, the expr...

Hypoxia induces Hif-1alpha and selects for loss of wild-type p53 function, both of which can promote tumor cell survival. We evaluated the ability of TRAIL to induce apoptosis of human tumor cell lines exposed to hypoxia. H460 lung cancer cells express low levels of Hif-1alpha, stabilize wild-type p53 during hypoxia, and undergo TRAIL-induced apoptosis. In U2OS osteosarcoma or PA1 ovarian terat...

The mechanism of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in cancer cells is not fully understood. Here, we show that the Akt survival pathway plays an important role in TRAIL resistance in human cancer cells. Specifically, we found that TRAIL treatment activates the Akt survival pathway and that inhibition of this pathway by the PI3K inhibitor LY294002 or knoc...