FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2017009058> ?p ?o ?g. }

• W2017009058 endingPage "2143" @default.
• W2017009058 startingPage "2121" @default.
• W2017009058 abstract "The clinical application of rituximab (chimeric mouse anti-human CD20 mAb, Rituxan, IDEC-C2B8), alone and/or combined with chemotherapy, has significantly ameliorated the treatment outcome of patients with relapsed and refractory low-grade or follicular non-Hodgkin's lymphoma (NHL). The exact in vivo mechanisms of action of rituximab are not fully understood, although antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis have been suggested. We have proposed that modifications of the cellular signaling pathways by rituximab may be crucial for its clinical response. The B-cell restricted cell surface phosphoprotein CD20 is involved in many cellular signaling events including proliferation, activation, differentiation, and apoptosis upon crosslinking. Monomeric rituximab chemosensitizes drug-resistant NHL cells via selective downregulation of antiapoptotic factors through the type II mitochondrial apoptotic pathway. Several signaling pathways are affected by rituximab which are implicated in the underlying molecular mechanisms of chemosensitization. ARL (acquired immunodeficiency syndrome (AIDS)-related lymphoma) and non-ARL cell lines have been examined as in vitro model systems. In ARL, rituximab diminishes the activity of the p38MAPK signaling pathway resulting in inhibition of the interleukin (IL)-10/IL-10R autocrine/paracrine cytokine autoregulatory loop leading to the inhibition of constitutive STAT-3 activity and subsequent downregulation of Bcl-2 expression leading to chemosensitization. Rituximab upregulates Raf-1 kinase inhibitor protein (RKIP) expression in non-ARL cells. Through physical association with Raf-1 and nuclear factor κB (NF-κB)-inducing kinase (NIK), RKIP negatively regulates two major survival pathways, namely, the extracellular signal-regulated kinase1/2 (ERK1/2) and the NF-κB pathways, respectively. Downmodulation of the ERK1/2 and NF-κB pathways inhibits the transcriptional activity of AP-1 and NF-κB transcription factors, respectively, both of which lead to the downregulation of Bcl-xL (Bcl-2 related gene (long alternatively spliced variant of Bcl-x gene)) transcription and expression and sensitization to drug-induced apoptosis. Bcl-xL-overexpressing cells corroborated the pivotal role of Bcl-xL in chemosensitization. The specificity of rituximab-mediated signaling and functional effects were corroborated by the use of specific pharmacological inhibitors. Many patients do not respond and/or relapse and the mechanisms of unresponsiveness are unknown. Rituximab-resistant B-NHL clones were generated to investigate the acquired resistance to rituximab-mediated signaling, and chemosensitization. Resistant clones display different phenotypic, genetic and functional properties compared to wild-type cells. This review summarizes the data highlighting a novel role of rituximab as a signal-inducing antibody and as a chemosensitizing agent through negative regulation of major survival pathways. Studies presented herein also reveal several intracellular targets modified by rituximab, which can be exploited for therapeutic and prognostic purposes in the treatment of patients with rituximab- and drug-refractory NHL." @default.
• W2017009058 created "2016-06-24" @default.
• W2017009058 creator A5010565662 @default.
• W2017009058 creator A5055490703 @default.
• W2017009058 date "2005-03-24" @default.
• W2017009058 modified "2023-10-17" @default.
• W2017009058 title "Cellular and molecular signal transduction pathways modulated by rituximab (rituxan, anti-CD20 mAb) in non-Hodgkin's lymphoma: implications in chemosensitization and therapeutic intervention" @default.
• W2017009058 cites W1481925502 @default.
• W2017009058 cites W1489062930 @default.
• W2017009058 cites W1499746632 @default.
• W2017009058 cites W1511416976 @default.
• W2017009058 cites W1512720088 @default.
• W2017009058 cites W1522731616 @default.
• W2017009058 cites W1524901905 @default.
• W2017009058 cites W1539571840 @default.
• W2017009058 cites W1568678893 @default.
• W2017009058 cites W156988820 @default.
• W2017009058 cites W1571475288 @default.
• W2017009058 cites W1573856597 @default.
• W2017009058 cites W1578536091 @default.
• W2017009058 cites W1580997941 @default.
• W2017009058 cites W1589026573 @default.
• W2017009058 cites W1591208477 @default.
• W2017009058 cites W1594335059 @default.
• W2017009058 cites W161930446 @default.
• W2017009058 cites W1633090059 @default.
• W2017009058 cites W1874291746 @default.
• W2017009058 cites W1892026381 @default.
• W2017009058 cites W1897592311 @default.
• W2017009058 cites W1898469614 @default.
• W2017009058 cites W1915689252 @default.
• W2017009058 cites W1964882341 @default.
• W2017009058 cites W1964956799 @default.
• W2017009058 cites W1965583590 @default.
• W2017009058 cites W1965985271 @default.
• W2017009058 cites W1966075310 @default.
• W2017009058 cites W1969484474 @default.
• W2017009058 cites W1971175458 @default.
• W2017009058 cites W1971915141 @default.
• W2017009058 cites W1971967721 @default.
• W2017009058 cites W1974283070 @default.
• W2017009058 cites W1976382352 @default.
• W2017009058 cites W1976385326 @default.
• W2017009058 cites W1977588072 @default.
• W2017009058 cites W1977983659 @default.
• W2017009058 cites W1978686430 @default.
• W2017009058 cites W1979419663 @default.
• W2017009058 cites W1983339176 @default.
• W2017009058 cites W1984035854 @default.
• W2017009058 cites W1984789674 @default.
• W2017009058 cites W1985460392 @default.
• W2017009058 cites W1985955648 @default.
• W2017009058 cites W1987013746 @default.
• W2017009058 cites W1987342520 @default.
• W2017009058 cites W1989480480 @default.
• W2017009058 cites W1990016924 @default.
• W2017009058 cites W1990206463 @default.
• W2017009058 cites W1990892742 @default.
• W2017009058 cites W1991686867 @default.
• W2017009058 cites W1992361007 @default.
• W2017009058 cites W1992990182 @default.
• W2017009058 cites W1993805759 @default.
• W2017009058 cites W1995355143 @default.
• W2017009058 cites W1995595768 @default.
• W2017009058 cites W1996405087 @default.
• W2017009058 cites W1996918021 @default.
• W2017009058 cites W1997208169 @default.
• W2017009058 cites W1999141617 @default.
• W2017009058 cites W2000652742 @default.
• W2017009058 cites W2002161324 @default.
• W2017009058 cites W2004329597 @default.
• W2017009058 cites W2006090885 @default.
• W2017009058 cites W2007436659 @default.
• W2017009058 cites W2010244981 @default.
• W2017009058 cites W2011894253 @default.
• W2017009058 cites W2012012527 @default.
• W2017009058 cites W2015788325 @default.
• W2017009058 cites W2016904449 @default.
• W2017009058 cites W2018011543 @default.
• W2017009058 cites W2019860775 @default.
• W2017009058 cites W2021812388 @default.
• W2017009058 cites W2021817265 @default.
• W2017009058 cites W2024282024 @default.
• W2017009058 cites W2027374210 @default.
• W2017009058 cites W2028016215 @default.
• W2017009058 cites W2028928387 @default.
• W2017009058 cites W2030519257 @default.
• W2017009058 cites W2030522563 @default.
• W2017009058 cites W2031330782 @default.
• W2017009058 cites W2031552402 @default.
• W2017009058 cites W2032361307 @default.
• W2017009058 cites W2032423298 @default.
• W2017009058 cites W2032454178 @default.
• W2017009058 cites W2033485934 @default.
• W2017009058 cites W2033493576 @default.
• W2017009058 cites W2033621701 @default.
• W2017009058 cites W2034371559 @default.
• W2017009058 cites W2035277855 @default.

• next