Cancers, Vol. 12, Pages 472: Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma
Cancers, Vol. 12, Pages 472: Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma
Cancers doi: 10.3390/cancers12020472
Authors:
Kamimura
Yokoo
Abe
Sakai
Nagoya
Kobayashi
Ohtsuka
Miura
Sakamaki
Kamimura
Miyamura
Nishina
Terai
Hepatocellular carcinoma (HCC) is a major global malignancy, responsible for >90% of primary liver cancers. Currently available therapeutic options have poor performances due to the highly heterogeneous nature of the tumor cells; recurrence is highly probable, and some patients develop resistances to the therapies. Accordingly, the development of a novel therapy is essential. We assessed gene therapy for HCC using a diphtheria toxin fragment A (DTA) gene-expressing plasmid, utilizing a non-viral hydrodynamics-based procedure. The antitumor effect of DTA expression in HCC cell lines (and alpha-fetoprotein (AFP) promoter selectivity) is assessed in vitro by examining HCC cell growth. Moreover, the effect and safety of the AFP promoter-selective DTA expression was examined in vivo using an HCC mice model established by the hydrodynamic gene delivery of the yes-associated protein (YAP)-expressing plasmid. The protein synthesis in DTA transfected cells is inhibited by the disappearance of tdTomato and GFP expression co-transfected upon the delivery of the DTA plasmid; the HCC cell growth is inhibited by the expression of DTA in HCC cells in an AFP promoter-selective manner. A signifi...
Source: Cancers - Category: Cancer & Oncology Authors: Kamimura Yokoo Abe Sakai Nagoya Kobayashi Ohtsuka Miura Sakamaki Kamimura Miyamura Nishina Terai Tags: Article Source Type: research
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