TITLE

Plasminogen fragment K1-5 improves survival in a murine hepatoceflular carcinoma model

AUTHOR(S)
Schmitz, Volker; Raskopf, Esther; Gonzalez-Carmona, Maria Angeles; Vogt, Annabelle; Robe, Chrstian; Leifeld, Ludger; Kornek, Miroslaw; Sauerbruch, Tilman; Caselmann, Wolfgang H.
PUB. DATE
February 2007
SOURCE
Gut;Feb2007, Vol. 56 Issue 2, p271
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: The prognosis of patients with hepatocellular carcinoma (HCC) remains poor, and new alternative treatments are needed. Aims: To comparatively test the angiostatic and antitumour effects of adenoviral gene transfer of angiostatin (PlgK1-4, amino acids 1-440) and full kringles 1-5 (PIgK1-5, amino acids 1-546) in a model of subcutaneously transferred HCC in mice. Methods: PIgK1-4 and PIgK1-5 were generated from human WtPlg cDNA and used for adenovirus construction. Vector function and angiostatic effects were confirmed in vitro and in vivo. Antitumoral efficacies of intratumoral vector injections were studied in a model of subcutaneously transferred HCC model. Results: Cell supernatants containing PIgK1-4 and PlgK1-5 reduced endothelial tube formation in vitro by about 30%, whereas WtPlg exerted no inhibitory effect. Endothelial cell infiltration in vivo was decreased by about 60%, but not in AdWtPlg-treated animals. Intratumoral treatment of subcutaneous HCC tumours inhibited growth by 40% for AdPIgK1-4 and 63% for AdPIgK1-5 in surviving mice 12 days after initiation of treatment, whereas treatment with AdWtPlg even led to accelerated growth. Although PIgK1-4 and PlgK1-5 have similar inhibitory effects on intratumoral microvessels, PlgK1-5 markedly improved the survival time compared with PIgK1-4. Conclusion: PI9K1-5 and PIgK1-4 effectively inhibited HCC growth. As PlgK1-5 could also prolong the survival time, inducing complete tumour elimination in half of the AdPIgK1 -5-treated mice, PIgK1-5 might be the most potential plasminogen fragment for treatment of experimental HCC.
ACCESSION #
24040272

 

Related Articles

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics