Self-assembled nanoparticles based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) were proposed earlier as a new drug delivery system. In the current work, we study antitumor activity of Amph-PVP-based self-assembled polymeric micelles covalently conjugated with receptor-specific TRAIL variant DR5-B (P-DR5-B). The Amph-PVP polymer was synthesized by developed one-step technique (Kulikov et ...

Abstract Acute kidney injury (AKI) exhibits high morbidity and mortality. Kidney molecule-1 (KIM1) is dramatically upregulated in renal tubules upon injury, acts as a biomarker for various diseases. However, the exact role underlying mechanism of KIM1 progression AKI remain elusive. Herein, we report that tubular specific knockout Kim1 attenuates cisplatin- or ischemia/reperfusion-induced male ...

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/death receptor 5 (DR5)-mediated cell death plays an important role in the elimination of tumor cells and transformed cells. Recently, recombinant TRAIL and agonistic anti-DR5 monoclonal antibodies have been developed and applied to cancer therapy. However, depending on the type of cancer, the sensitivity to TRAIL has been reportedl...

PURPOSE Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is clinically evaluated as novel anticancer drug. rhTRAIL-DR5, a rhTRAIL variant that specifically binds to DR5 receptor, has recently been developed. We investigated whether rhTRAIL-DR5 is more efficient than rhTRAIL in combination with cisplatin in DR5-expressing human A2780 ovarian cancer cells. DES...

Death receptor DR5 (DR5/TRAIL-R2) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we showed that curcumin, a plant product containing the phenolic phytochemical, is a potent enhancer of TRAIL-induced apoptosis through upregulation of DR5 expression. Both treatment with DR5/Fc chimeric protein and silencing of DR5 exp...

Death Receptor 5 (DR5) is known to be an important anti-cancer drug target. TRAIL is a natural ligand of DR5, but its drug action is limited because of several factors. A few agonistic ligands were identified as TRAIL-DR5 axis modulators, which enhance the cellular apoptosis. Literature suggest that quinacrine (QC) acts as a DR5 agonistic ligand. However, the detailed mechanism explaining how Q...

Nonalcoholic steatohepatitis is characterized by hepatic steatosis, elevated levels of circulating free fatty acids (FFA), endoplasmic reticulum (ER) stress, and hepatocyte lipoapoptosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 5 (DR5) is significantly elevated in patients with nonalcoholic steatohepatitis, and steatotic hepatocytes demonstrate increased s...

Here we show a novel mechanism by which FLICE-like inhibitory protein (c-FLIP) regulates apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and one of its receptors, DR5. c-FLIP is a critical regulator of the TNF family of cytokine receptor signaling. c-FLIP has been postulated to prevent formation of the competent death-inducing signaling complex (DISC) ...