Bevacizumab exacerbates sinusoidal obstruction syndrome (SOS) in the animal model and increases MMP 9 production

Oncotarget
Azin JafariSteffen Manekeller

Abstract

Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. After MCT administration 67% of animals developed SOS. GOT serum concentration significantly increased in animals developing SOS (p < 0.001). Subsequent to MCT administration 100% of animals treated with Anti-VEGF developed SOS. In contrast, animals receiving VEGF developed SOS merely in 40% while increasing the VEGF dose led to a further decrease in SOS development to 25%. MMP 9 concentration in animals developing SOS was significantly higher compared to controls (p < 0,001). Additional treatment with Anti-VEGF increased the MMP 9 concentration significantly (p < 0,05). Preservation of liver function is a central goal in both curative and palliative treatment phases of patients with CRC. Thus, knowledge about hepatotoxic side effects of chemotherapeutic and biological agents is crucial...Continue Reading

References

Nov 6, 2007·Seminars in Liver Disease·Laurie D DeLeve
Nov 9, 2010·Clinics in Liver Disease·Laura Rubbia-Brandt
Aug 18, 2017·International Journal of Molecular Sciences·Deok-Hoon KongSukmook Lee

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Citations

Jun 18, 2020·Therapeutic Advances in Gastroenterology·Alexandra Gangi, Shelly C Lu
Jun 11, 2019·Expert Review of Clinical Pharmacology·Zhongguang Chen, Lili Jiang
Oct 31, 2020·Toxicology Letters·Fumisato OtakaMasataka Majima

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Methods Mentioned

BETA
surgical resection
ELISA
light microscopy

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