Abstract : Targeted cancer therapy provides the basis for the arrest of tumor growth in aggressive pancreatic carcinoma; however, a number of protein‐based targeted toxins lack efficacy due to insufficient endosomal escape after being ...
Book Title: Targeted Dianthin is a Powerful Toxin to Treat Pancreatic Carcinoma when Applied in Combination with the Glycosylated Triterpene SO1861
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Published on 2017 by
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Book is About: Carcinoma treatment
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Abstract : Targeted cancer therapy provides the basis for the arrest of tumor growth in aggressive pancreatic carcinoma; however, a number of protein‐based targeted toxins lack efficacy due to insufficient endosomal escape after being endocytosed. Therefore, we tested a fusion protein of the ribosome‐inactivating protein dianthin and human epidermal growth factor in combination with a glycosylated triterpene (SO1861) that serves as an endosomal escape enhancer. In vitro investigations with the pancreatic carcinoma cell lines BxPC‐3 and MIA PaCa‐2 revealed no significant differences to off‐target cells in the half maximal inhibitory concentration (IC50 ) for the fusion protein. In contrast, combination with SO1861 decreased the IC50 for BxPC‐3 cells from 100 to 0.17 nm, whereas control cells remained unaffected. Monotherapy of BxPC‐3 xenografts in CD‐1 nude mice led to a 51.7% average reduction in tumor size (40.8 mm 3 ) when compared to placebo; however, combined treatment with SO1861 resulted in a more than 13‐fold better efficacy (3.0 mm 3 average tumor size) with complete regression in 80% of cases. Immunohistochemical analyses showed that tumor cells with lower target receptor expression are, in contrast to the combination therapy, able to escape from the monotherapy, which finally results in tumor growth. At the effective concentration, we did not observe liver toxicity and saw no other side effects with the exception of a reversible skin hardening at the SO1861 injection site, alongside an increase in platelet counts, plateletcrit, and platelet distribution width. In conclusion, combining a targeted toxin with SO1861 is proven to be a very promising approach for pancreatic cancer treatment. Abstract : We investigated a fusion protein of the plant toxin dianthin and human epidermal growth factor together with a glycosylated triterpene (SO1861) to enhance endosomal escape. Monotherapy of pancreatic carcinoma xenografts in nude mice led to 51.7% tumor reduction (40.8 mm 3 ); however, combined treatment with SO1861 resulted in a 13‐fold better efficacy (3.0 mm 3 ) with complete regression in 80% of cases.
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