Antivascular therapy for multidrug-resistant ovarian tumors by macitentan, a dual endothelin receptor antagonist.

Translational Oncology
Sun-Jin KimI J Fidler

Abstract

Endothelin receptors (ETRs) are often overexpressed in ovarian tumors, which can be resistant to conventional therapies. Thus, we investigated whether blockage of the ETR pathways using the dual ETR antagonist macitentan combined with taxol or cisplatinum can produce therapy for orthotopically growing multidrug-resistant (MDR) human ovarian carcinoma. In several studies, nude mice were injected in the peritoneal cavity with HeyA8-MDR human ovarian cancer cells. Ten days later, mice were randomized to receive vehicle (saline), macitentan (oral, daily), taxol (intraperitoneal, weekly), cisplatinum (intraperitoneal, weekly), macitentan plus taxol, or macitentan plus cisplatinum. Moribund mice were killed, and tumors were collected, weighed, and prepared for immunohistochemical analysis. The HeyA8-MDR tumors did not respond to taxol, cisplatinum, or macitentan administered as single agents. In contrast, combination therapy with macitentan and taxol or macitentan and cisplatinum significantly decreased the tumor incidence and weight and significantly increased the survival of mice and their general condition. Multiple immunohistochemical analyses revealed that treatment with macitentan and macitentan plus taxol or cisplatinum inhibi...Continue Reading

References

Nov 1, 1995·Journal of the National Cancer Institute·I J Fidler
Aug 10, 1995·The New England Journal of Medicine·E R Levin
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
Nov 18, 1993·The New England Journal of Medicine·S A Cannistra
Mar 5, 1999·Clinical and Experimental Pharmacology & Physiology·R G Goldie
Apr 4, 2000·American Journal of Respiratory Cell and Molecular Biology·S I AhmedP J Woll
Jun 22, 2000·The Prostate·G Pirtskhalaishvili, J B Nelson
Jun 29, 2000·American Journal of Respiratory Cell and Molecular Biology·B HocherF Theuring
Sep 8, 2000·Journal of Cardiovascular Pharmacology·M Clozel
Nov 15, 2000·Journal of Cardiovascular Pharmacology·L P EberlL Juillerat-Jeanneret
Feb 4, 2003·Nature Reviews. Cancer·Joel NelsonPerry Nisen
Jul 2, 2003·Nature Reviews. Cancer·Roshan Agarwal, Stan B Kaye
Jul 8, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Premal H ThakerAnil K Sood
Jun 8, 2006·Journal of the National Cancer Institute·Sun-Jin KimIsaiah J Fidler
Sep 21, 2006·Neoplasia : an International Journal for Oncology Research·Ardavan AkhavanBeth R Pflug
Mar 6, 2007·Critical Reviews in Oncology/hematology·David J Stewart
Sep 11, 2008·The Journal of Pharmacology and Experimental Therapeutics·Marc IglarzMartine Clozel
Feb 4, 2009·American Journal of Respiratory Cell and Molecular Biology·Priya KulasekaranJeffrey C Horowitz
Feb 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Laura RosanòAnna Bagnato
May 29, 2009·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Jul 9, 2010·Cancer Research·James E Talmadge, Isaiah J Fidler
Dec 21, 2010·Molecular Pharmaceutics·Payam ZahediChristine Allen
Jan 15, 2011·British Journal of Pharmacology·A BagnatoJ Growcott

❮ Previous
Next ❯

Citations

Dec 4, 2013·Drugs·Trina Patel, Kate McKeage
Sep 4, 2015·Cancer Metastasis Reviews·Isaiah J Fidler, Margaret L Kripke
Jan 29, 2013·European Journal of Pharmacology·Johanna WeissWalter Emil Haefeli
Oct 8, 2014·Archivum Immunologiae Et Therapiae Experimentalis·Agata KowalczykAnna Goraca
Jul 31, 2016·Journal of Experimental & Clinical Cancer Research : CR·Laura Rosanò, Anna Bagnato
Jan 25, 2014·The Annals of Pharmacotherapy·Irene S HongLinda M Catanzaro
Feb 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Francesca Di ModugnoLaura Rosanò
Jul 26, 2013·Nature Reviews. Cancer·Laura RosanòAnna Bagnato
Aug 2, 2017·Expert Opinion on Therapeutic Targets·Laura RosanòAnna Bagnato
Jul 18, 2020·Future Cardiology·Rodrigo ZebadúaTomás Pulido
Jul 15, 2017·Cell Death and Differentiation·Roberta CianfroccaAnna Bagnato
Jan 29, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Laura Rosanò, Anna Bagnato
Jan 11, 2021·Journal of Experimental & Clinical Cancer Research : CR·Piera TocciAnna Bagnato

❮ 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