Antitumor activity of fibroblast growth factor receptor 3-specific immunotoxins in a xenograft mouse model of bladder carcinoma is mediated by apoptosis

Molecular Cancer Therapeutics
Jorge L Martínez-TorrecuadradaJ Ignacio Casal

Abstract

Human single-chain Fv directed against fibroblast growth factor receptor 3 (FGFR3) have been shown to block proliferation of RT112 bladder carcinoma cells in vitro. Here, we examined the ability of the recombinant gelonin toxin (rGel) to enhance this inhibitory effect in vitro and in vivo on the bladder cancer cell line RT112 and the corresponding xenografts. Immunotoxins were genetically engineered by fusing FGFR3-specific Fv fragments (3C) to the NH(2) terminus of rGel and expressed as a soluble protein in Escherichia coli. The 3C/rGel fusion construct showed an IC(50) of 200 nmol/L against log-phase RT112 cells compared with 1,500 nmol/L for free rGel. Immunofluorescence studies showed that the 3C/rGel construct internalized rapidly into the cytoplasm of RT112 cells within 1 h of exposure. The mechanism of immunotoxin-induced cell death was found to be mediated by apoptosis. RT112 tumor xenografts in severe combined immunodeficient mice treated with 50 mg/kg 3C/rGel exhibited considerable growth delay relative to control tumors and a significant reduction of 55% to 70% in mean tumor size. Immunohistochemical analysis showed that tumors from mice treated with 3C/rGel displayed considerable apoptotic damage compared with contr...Continue Reading

References

Jun 1, 1995·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M G RosenblumL Cheung
Jan 19, 1996·The Journal of Biological Chemistry·S Santos-OcampoD M Ornitz
Oct 31, 1997·Clinical & Experimental Metastasis·T A TetzkeZ Parandoosh
Jun 8, 2001·The American Journal of Pathology·C BillereyF Radvanyi
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Liesbeth M VeenendaalMichael G Rosenblum
Dec 4, 2002·European Journal of Human Genetics : EJHG·Bas W G van RhijnFrancois Radvanyi
May 14, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bas W G van RhijnEllen C Zwarthoff
Dec 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jay Y ChoWilliam A Horton
Feb 12, 2004·British Journal of Haematology·Joshua L PatersonA Keith Stewart
Feb 19, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P Boyle, J Ferlay
May 3, 2005·Cytokine & Growth Factor Reviews·Richard Grose, Clive Dickson
Aug 20, 2005·Nature Reviews. Cancer·Xue-Ru Wu
Sep 8, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jorge Martínez-TorrecuadradaJ Ignacio Casal
Sep 9, 2005·World Journal of Gastroenterology : WJG·Wei-Hua QiuYun Yen
Oct 26, 2005·Neoplasia : an International Journal for Oncology Research·Khalid A MohamedaliMichael G Rosenblum
Jan 21, 2006·Nature Reviews. Drug Discovery·David SchramaJürgen C Becker
Mar 4, 2006·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Jun 17, 2006·Cancer Research·Ted C ChuMatthew Levy
Jun 24, 2006·Nature Reviews. Cancer·Ira PastanRobert J Kreitman
Aug 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Silvia HernándezFrancisco X Real
Aug 18, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiaohua XinCarla C Heise
Oct 5, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F G E Perabo, S C Müller
Nov 17, 2006·Cancer Research·Khalid A MohamedaliMichael G Rosenblum

❮ Previous
Next ❯

Citations

Mar 26, 2010·Expert Reviews in Molecular Medicine·Courtney PollardDan Theodorescu
Feb 28, 2009·Nature Reviews. Drug Discovery·Andrew Beenken, Moosa Mohammadi
Jul 3, 2010·Journal of Gastroenterology and Hepatology·Xin-Xin ZhouCheng-Fu Xu
Aug 18, 2012·Advances in Urology·Erica di MartinoMargaret A Knowles
Jun 12, 2010·Cytogenetic and Genome Research·B J Henson, S M Gollin
Apr 22, 2009·The Journal of Clinical Investigation·Jing QingAvi Ashkenazi
Feb 13, 2014·Applied Microbiology and Biotechnology·Xiguang ZhangYechen Xiao
Oct 7, 2014·Expert Opinion on Investigational Drugs·Clarisse R MazzolaJoseph Chin
Mar 29, 2014·Expert Opinion on Drug Discovery·Paula A OliveiraCarmen Vasconcelos-Nóbrega
Jun 23, 2009·Expert Opinion on Drug Delivery·M WirthF Gabor
Dec 18, 2009·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Oct 17, 2015·Analytical and Bioanalytical Chemistry·Riikka PeltomaaMaría Cruz Moreno-Bondi
Jul 18, 2015·Chinese Journal of Cancer·Meiqi ZengOu Sha
Jan 26, 2012·Biochimica Et Biophysica Acta·Imran AhmadHing Y Leung
Jun 17, 2014·The Journal of Urology·Rafal TuroMargaret A Knowles
Jul 8, 2011·Journal of Experimental & Clinical Cancer Research : CR·Xu WeiLiu Zheng
Jul 7, 2016·Future Oncology·Erica di MartinoMargaret A Knowles
Jul 7, 2010·International Braz J Urol : Official Journal of the Brazilian Society of Urology·Xiaoping Yang, Thomas W Flaig
Nov 5, 2010·Molecular Cancer Research : MCR·Ellen Margrethe HaugstenJørgen Wesche

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bladder Carcinoma In Situ

Bladder Carcinoma In Situ is a superficial bladder cancer that occurs on the surface layer of the bladder. Discover the latest research on this precancerous condition in this feed.

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