Ann Rev Cell Dev Biol 14:111–136ĭumitru CA, Gulbins E (2006) TRAIL activates acid sphingomyelinase via a redox mechanism and releases ceramide to trigger apoptosis. Curr Opin Cell Biol 9:534–542īrown DA, London E (1998) Functions of lipid rafts in biological membranes. Harder T, Simons K (1997) Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains. Simons K, Ikonen E (1997) Functional rafts in cell membranes. J Exp Med 186:1165–1170Įmery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. Cancer Res 59:2770–2775ĭegli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang CP, DuBose RF, Goodwin RG, Smith CA (1997) Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. Wu GS, Burns TF, Zhan Y, Alnemri ES, El-Deiry WS (1999) Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor. Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J (1997) TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM (1997) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Gene Ther 9:1262–1270ĭuiker EW, Mom CH, de Jong S, Willemse PH, Gietema JA, van der Zee AG, de Vries EG (2006) The clinical trail of TRAIL. Zhang L, Gu J, Lin T, Huang X, Roth JA, Fang B (2002) Mechanisms involved in development of resistance to adenovirus-mediated proapoptotic gene therapy in DLD1 human colon cancer cell line. Ursini-Siegel J, Zhang W, Altmeyer A, Hatada EN, Do RK, Yagita H, Chen-Kiang S (2002) TRAIL/Apo-2 ligand induces primary plasma cell apoptosis. Janssen EM, Droin NM, Lemmens EE, Pinkoski MJ, Bensinger SJ, Ehst BD, Griffith TS, Green DR, Schoenberger SP (2005) CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death. Hayakawa Y, Screpanti V, Yagita H, Grandien A, Ljunggren HG, Smyth MJ, Chambers BJ (2004) NK cell TRAIL eliminates immature dendritic cells in vivo and limits dendritic cell vaccination efficacy. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (1997) The receptor for the cytotoxic ligand TRAIL. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. These data show that local release of ceramide potentiates very low, otherwise inactive doses of TRAIL that may represent a novel therapeutic concept to treat tumors. Genetic deficiency of the ASM abrogated doxorubicin-induced ceramide release, as well as clustering of DR5 and apoptosis induced by the combined treatment of doxorubicin and TRAIL. The latter served DR5 to cluster after application of very low doses of TRAIL in combination with doxorubicin. Ceramide production was induced by application of sub-toxic doses of doxorubicin that resulted in an activation of the acid sphingomyelinase (ASM), release of ceramide and formation of ceramide-enriched membrane platforms. Here, we employed this concept to convert doses of subtherapeutic TRAIL that were unable to release ceramide and kill leukemic B-cells or ex vivo T lymphocytes, into a very effective apoptotic stimulus. You can read the full Dead Cells review here.Previous studies indicated that signalling via CD95 and DR5 is greatly enhanced by the formation of ceramide-enriched membrane platforms. This is the kind of game that can last you forever, you just have to let it beat you in the head a few times. It is here that Dead Cells lets you know that it is just the beginning, there are a few more go around yet, and each one gets harder and harder. When you finally take out the final boss you will be elated. Every success will fill you with endorphins, every failure will inspire you to get better. With incredibly satisfying gameplay, a constant stream of unlocks, and a world that challenge every cell of your being, Dead Cells is a must own for anyone who likes even one aspect of what has been mentioned here. Stepping back to 2018, Jason wrote in our review: The new biomes will help to shake up the mid-game runs for those who’ve mastered the game over the past few years. The paid expansion will introduce two new mid-game biomes – The Fractures Shrines and The Undying Shores – a new boss – The Scarecrow – and a slew of new weapons.
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