Preclinical differentiation between apparently safe and potentially hepatotoxic applications of TRAIL either alone or in combination with chemotherapeutic drugs

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Tom M GantenHenning Walczak

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) exhibits potent antitumor activity on systemic administration in nonhuman primates without deleterious side effects for normal tissue. However, there is a controversy about the potential toxicity of TRAIL on human hepatocytes. The use of different recombinant TRAIL forms only partially explains the contradicting reports on TRAIL sensitivity in primary human hepatocytes (PHH). To clarify this issue, we comprehensively tested four different recombinant forms of TRAIL for their apoptosis-inducing capacity on PHH obtained from a total of 55 human livers between day 1 and day 8 of in vitro culture. One day after single-cell isolation, all but one recombinant form of TRAIL [i.e., an untagged form of TRAIL (TRAIL.0)] induced apoptosis in PHH. Apoptosis induction by TRAIL in these cells could only be fully inhibited by concomitant blockade of TRAIL receptor 1 and TRAIL receptor 2. At day 4 of in vitro culture, when surrogate markers indicated optimal hepatocyte in vitro function, only high doses of cross-linked FLAG-TRAIL killed PHH whereas the other three recombinant TRAIL forms did not. Strikingly, cotreatment of day 4 PHH with cisplatin sensitized for TRAIL-induce...Continue Reading

References

Sep 1, 1984·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·F BalletR Infante
Apr 4, 1997·Science·G PanV M Dixit
Oct 6, 1997·The EMBO Journal·H WalczakC T Rauch
Oct 7, 1997·The Journal of Experimental Medicine·M A Degli-EspostiC A Smith
Oct 27, 1997·The Journal of Biological Chemistry·C ScaffidiM E Peter
Jun 11, 1998·The Journal of Biological Chemistry·J G EmeryP R Young
Jul 20, 1999·The Journal of Clinical Investigation·A AshkenaziR H Schwall
Apr 3, 2001·Nature Medicine·D LawrenceA Ashkenazi
Dec 19, 2002·Cytokine & Growth Factor Reviews·Tudor M Baetu, John Hiscott
Mar 26, 2003·Cell Death and Differentiation·H N LeBlanc, A Ashkenazi
May 24, 2003·Journal of Hepatology·Henning Schulze-BergkamenUlrike Protzer
Aug 30, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tongyu LinBingliang Fang
Feb 24, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alberto BallestreroFranco Patrone
May 20, 2004·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Diana C SpieringsSteven de Jong
May 26, 2004·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Sharmila Shankar, Rakesh K Srivastava
Oct 27, 2004·Cancer Science·Hideo YagitaKo Okumura
Dec 3, 2004·Cancer Research·Chunhai HaoNorman M Kneteman
Mar 1, 2005·Cytokine & Growth Factor Reviews·Harald WajantKlaus Pfizenmaier
Jul 23, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tom M GantenHenning Walczak

❮ Previous
Next ❯

Citations

Dec 26, 2007·Pathology Oncology Research : POR·Matthias FelberJames F Beck
Apr 18, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ronald KoschnyTom M Ganten
Aug 15, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Tom M GantenHenning Walczak
Dec 5, 2012·Applied Microbiology and Biotechnology·Li Qiang PanShu Qing Chen
Feb 6, 2009·Apoptosis : an International Journal on Programmed Cell Death·Thomas Newsom-DavisHenning Walczak
Oct 1, 2013·Trends in Molecular Medicine·Daniel W Stuckey, Khalid Shah
Sep 4, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sunetra RaySanjiv S Gambhir
Nov 8, 2008·Nature Reviews. Drug Discovery·Avi Ashkenazi
Jul 20, 2010·Oncogene·M M Lovric, C J Hawkins
Jan 19, 2008·Cell Death and Differentiation·M TodaroG Stassi
Jan 15, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maria Eugenia Guicciardi, Gregory J Gores
Dec 15, 2007·The Journal of Clinical Investigation·Anne Grosse-WildeHenning Walczak
Jun 5, 2008·The Journal of Clinical Investigation·Avi Ashkenazi, Roy S Herbst
Mar 29, 2014·PLoS Computational Biology·Fabian KonrathDagmar Kulms
Feb 28, 2009·PloS One·Challagundla K BabuStacey A Rizza
Sep 28, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ute FischerKlaus Schulze-Osthoff
Jul 9, 2008·World Journal of Gastroenterology : WJG·Henning Schulze-BergkamenMarkus Moehler
Aug 26, 2014·Annual Review of Cell and Developmental Biology·Avi Ashkenazi, Guy Salvesen
Mar 23, 2010·Cellular and Molecular Life Sciences : CMLS·R WeinlichG P Amarante-Mendes
Dec 22, 2007·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·A M ChromikU Mittelkötter
Oct 3, 2007·Expert Opinion on Therapeutic Targets·Delphine MérinoOlivier Micheau
Mar 22, 2007·Expert Opinion on Therapeutic Targets·Georg Häcker, Stefan A Paschen
Sep 8, 2010·Expert Opinion on Therapeutic Targets·Junaid Abdulghani, Wafik S El-Deiry
Feb 13, 2016·Monoclonal Antibodies in Immunodiagnosis and Immunotherapy·Xiaofeng ChengMinping Zhang
Feb 27, 2009·Expert Opinion on Investigational Drugs·Patricia Moretto, Sébastien J Hotte
Oct 8, 2014·Journal of Neuropathology and Experimental Neurology·Ronald KoschnyTom M Ganten
Jul 10, 2012·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Raúl OrtizAntonia Aranega
Dec 10, 2009·Molecular Aspects of Medicine·Gregory MellierShazib Pervaiz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

© 2022 Meta ULC. All rights reserved