Nimotuzumab enhances temozolomide-induced growth suppression of glioma cells expressing mutant EGFR in vivo

Cancer Medicine
Yusuke NittaM Nagane

Abstract

A mutant form of epidermal growth factor receptor (EGFR), EGFRvIII, is common in glioblastoma (GBM) and confers enhanced tumorigenic activity and drug resistance. Nimotuzumab, an anti-EGFR antibody, has shown preclinical and clinical activity to GBM, but its specific activity against EGFRvIII has not been fully investigated. Human glioma U87MG or LNZ308 cells overexpressing either wild-type (wt) EGFR or EGFRvIII were treated with nimotuzumab, temozolomide, or both. Expression and phosphorylation status of molecules were determined by Western blot analysis. Methylation status of promoter region of O(6) -methylguanine-DNA methyltransferase (MGMT) was detected by methylation-specific PCR. Antitumor activity was tested using nude mice bearing either subcutaneous or intracerebral xenografts along with analyses of EGFR phosphorylation status, proliferation, apoptosis, and vessel density. Nimotuzumab treatment resulted in reduction of EGFRvIII tyrosine phosphorylation with a decrease in Akt phosphorylation that was greater than that of wtEGFR. Correspondingly, antitumor effects, growth suppression and survival elongation, were more significant in mice bearing either subcutaneous or intracerebral tumor expressing EGFRvIII than in those...Continue Reading

References

May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A J EkstrandV P Collins
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·R NishikawaH J Huang
Jan 2, 1994·International Journal of Cancer. Journal International Du Cancer·J SchlegelM Kiessling
Jul 13, 2002·Expert Review of Anticancer Therapy·S J Danson, M R Middleton
Sep 19, 2002·International Journal of Cancer. Journal International Du Cancer·Tania Crombet-RamosAlicia Viloria-Petit
May 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tania CrombetAgustín Lage
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Feb 10, 2006·The New England Journal of Medicine·James A BonnerK Kian Ang
Feb 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alba A BrandesRoger Stupp
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Jun 6, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·B NeynsJ De Greve
Jun 30, 2009·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Dani S Bidros, Michael A Vogelbaum
Jul 25, 2009·Expert Opinion on Biological Therapy·William Kells Boland, Gwyn Bebb
Jun 1, 2010·Neuro-oncology·Sandeep KunwarUNKNOWN PRECISE Study Group
Dec 22, 2010·Expert Opinion on Biological Therapy·Maura MassiminoGudrun Fleischhack
Mar 23, 2011·International Journal of Cancer. Journal International Du Cancer·Jörg FelsbergUNKNOWN German Glioma Network
Jul 26, 2011·Neuro-oncology·T J MacDonaldC M Kramm
Oct 10, 2012·Expert Opinion on Biological Therapy·Udo BodeGudrun Fleischhack
Jan 27, 2015·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Manfred WestphalTorsten Pietsch

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Citations

May 14, 2020·Expert Opinion on Investigational Drugs·Maria B Garcia-FabianiMaria G Castro
Mar 20, 2018·Oncology Letters·Fernando Francisco Borges ResendeRicardo Titze-de-Almeida
Oct 18, 2018·Clinical and Translational Medicine·Debarati GhoshSonali Bhattacharjee
Apr 17, 2018·Acta Biochimica Et Biophysica Sinica·Xin ChenBin Hao
Feb 13, 2021·AAPS PharmSciTech·Kanawat WiwatchaitaweeAliasger K Salem
May 1, 2021·Cancers·Elisabete Cruz Da SilvaLaurence Choulier
Nov 2, 2021·Biological & Pharmaceutical Bulletin·Ratna Dini HaryuniHiroaki Sakurai

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Methods Mentioned

BETA
xenografts
PCR

Software Mentioned

Gunma LI
SPSS

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