title: Regional therapy with DTA-H19 vector suppresses growth of colon adenocarcinoma metastases in the rat liver.
abstract: Curative surgery is possible in barely 10% of patients with colorectal liver metastases and combined treatment modalities scarcely improve survival in this group of patients. Hence, investigations of new therapeutic modalities are crucial. Overexpression of the H19 gene in liver metastases points to H19 as a target for cancer gene therapy. Here we have evaluated the possibility of regional intra-arterial treatment of liver meta-stases with the DTA-H19 plasmid. Intra-arterial treatment of a total dose of 2.5 mg (repeated injections of 500 µg DTA-H19 plasmid each dose after the first injection of 1000 µg) caused a significant delay in the tumor growth compared to control group. All of the tumors treated with the control vector increased in size, whereas 35.7% of the tumors in the groups treated with a total amount of 2.5 mg DTA-H19 plasmid shrank in size. The present study showed that the DTA-H19 plasmid administered intra-arterially significantly delayed the tumor growth and even resulted in tumor regression in high percentage of the treated animals with liver metastases of colon cancer. Since human liver metastases demonstrated overexpression of the H19 gene, regional administration of the plasmid seems to be a promising therapeutic approach.
authors.affiliation: Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel. vladimir.sorin@gmail.com
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sorin
authors.forename: Patricia
authors.initials: P
authors.lastname: Ohana
authors.forename: Aya
authors.initials: A
authors.lastname: Mizrahi
authors.forename: Imad
authors.initials: I
authors.lastname: Matouk
authors.forename: Tatiana
authors.initials: T
authors.lastname: Birman
authors.forename: Abraham
authors.initials: A
authors.lastname: Hochberg
authors.forename: Abraham
authors.initials: A
authors.lastname: Czerniak
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary* / Q000628:therapy*; D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008297:Male; D010477:Perfusion; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D051381:Rats; D014161:Transduction, Genetic
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated