Efficient and cancer-selective gene transfer to hepatocellular carcinoma in a rat using adenovirus vector with iodized oil esters

Abstract

Gene therapy for cancer requires efficient, selective gene transfer to cancer cells. In gene therapy for hepatocellular carcinoma ( HCC ) , gene transfer is efficient for small tumors, but not for large tumors. The delivery of anticancer agents and of iodized oil esters as embolic agents through tumor -feeding arteries is known as transarterial embolization. We speculate that genes may be efficiently and selectively transferred for HCC using iodized oil esters because these esters may remain together with a genetic vector within HCC selectively. Hence, we have studied the effect of iodized oil esters on adenovirus vector -mediated gene transfer for HCC in vivo. A rat model of HCC induced with diethylnitrosamine and phenobarbital was injected with either AxCALacZ, which expresses the -galactosidase of Escherichia coli, or AxCALacZ and iodized oil esters into the hepatic artery. Histological comparisons revealed that the -galactosidase expression in the rats with HCC injected with AxCALacZ and iodized oil esters was greater ( P < .0001 ) in small tumors ( P = .0046 ) and large tumors ( P = .0023 ) , and more selective ( P = .0229 ) than in only AxCALacZinjected rats. These results suggest that iodized oil esters are injected into hepatic artery together with adenovirus vector, and that genes may be efficiently and cancer -selectively transferred to HCC. Cancer Gene Therapy ( 2001 ) 8, 713 -718

Synergistic anticancer effect of rAd/P53 combined with 5-fluorouracil or iodized oil in the early therapeutic response of human colon cancer in vivo

“…Similar results were observed in phase I/II clinical studies of NSCLC or advanced breast cancer patients receiving intratumoral Ad-p53 injections combined with chemotherapy (Roth, 2006). The hepatic arterial infusion of an emulsion of iodized oil and Ad-p53 causes exogenous wt-p53 expression (Shiba et al, 2001). An in vitro study indicated that adenovirus-mediated p53 gene transfer promotes G 1 -phase arrest and cell apoptosis, thereby sensitizing hepatocellular carcinoma cells to heavy-ion irradiation (Liu et al, 2007) or CaSki human cervical cancer cells to photodynamic therapy (Lim et al, 2006).…”

Enhancement of p53 gene transfer efficiency in hepatic tumor mediated by transferrin receptor through trans-arterial delivery

“…15,40 Likewise, some attempts to apply chemotherapy or embolotherapy via tumor artery infusion have been made to obtain optimal effectiveness of antitumor therapy. [40][41][42][43] In summary, a combined approach of the Tf-TfR system with interventional catheter techniques enhanced the efficiency of p53 gene transfer to hepatic tumor in rabbit VX2 tumor models. The dual-target-oriented gene delivery may be an effective means for therapeutic gene therapy for human hepatocarcinoma.…”

A Novel Contrast Medium Detects Increased Permeability of Rat Injured Carotid Arteries in Magnetic Resonance T2 Mapping Imaging

“…In this sense, our contrast medi- um is quite different from other iron nanoparticles that accumulate at the lesion by phagocytosis 14) because a large amount of other iron nanoparticles are required to detect vascular lesions. Finally, this drug delivery system theoretically accommodates both contrast medium and agent for treatment, therefore enabling us to simultaneously detect and treat vascular lesions 25,26) . Furthermore, this particle can be modified to deliver agents to the target tissue more precisely 27) .…”