JX-594 is a targeted oncolytic poxvirus that is designed to eradicate cancer cells having cell-cycle defects, through replication, cell lysis, and spread within tumors; oncolysis-induced tumor vascular shutdown and immunostimulation are augmented by granulocyte monocyte-colony-stimulating factor (GM-CSF) transgene expression. We have previously shown, in animal models of hepatocellular carcinoma (HCC), that JX-594 is a promising anticancer agent. We tested JX-594 in three patients with advanced refractory hepatitis B virus (HBV)-associated HCC through intratumoral administration. JX-594 treatment was well-tolerated and resulted in antitumoral efficacy in all three patients, despite the presence of high levels of neutralizing antibodies. JX-594 replication, its release into the circulation, distant tumor targeting were demonstrated. JX-594 administration resulted in the induction of antivascular cytokines, and was associated with tumor vascular shutdown. We also showed, for the first time, that oncolytic virotherapy can suppress underlying HBV replication in HCC patients, and that tumor tissue could be the primary source of acute HBV replication and acute post-treatment HBV release. JX-594 treatment in HBV-associated HCC warrants further clinical testing; a Phase II trial is underway.
Hypereosinophilic syndrome may cause eosinophil-related tissue damage to various organs. The purpose of this paper is to describe sonographic findings in 13 patients with hypereosinophilia in whom the liver was involved. The diagnosis in these 13 patients was based on liver biopsy in seven patients with bone marrow biopsy in six patients. Eight patients had hypereosinophilic syndrome and five patients had clonorchiasis. All 13 patients had mild to marked hepatomegaly. Seven of 13 patients showed multiple round or oval hypoechoic (n = 6) or variably echogenic (n = 1) lesions measuring 1 to 2 cm with poorly defined margins in both lobes of the liver. Four patients had one or two hypoechoic lesions 3 to 4 cm in size, with geographic pattern and poorly defined margins. Two patients showed diffuse hepatomegaly with increased parenchymal echogenicity. The number of lesions and the extent of diffuse lesions seem to be proportional to the degree of eosinophilia. Hypereosinophilia may produce multiple small focal hepatic lesions or diffuse segmental or lobar echogenic lesions simulating primary or metastatic tumor of the liver.
The purpose of this study was to investigate the image quality and radiation dose of triple rule-out computed tomography (TROCT) using a 320-row-detector volume CT system to compare the wide-volume and helical modes of this CT system. Sixty-four patients with noncritical chest pain were allocated to one of 2 groups according to the type of CT examination mode used. Group 1 patients were examined using the wide-volume (non-spiral) mode and group 2 patients were examined using the 160-detector row helical mode, with the same contrast injection protocol in both methods [biphasic injection protocol; injection rate of 4 ml/s, median volume, 70 ml (range 65-100 ml)]. Attenuations of the pulmonary trunk, ascending aorta, and coronary arteries were measured in Hounsfield units; a subjective overall patient-based image quality score of 1-3 was awarded to each study. Effective doses, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Average effective dose was significantly lower in group 1 than group 2 (9.7 ± 5.1 vs. 16 ± 5.9 mSv, P < 0.001). The mean attenuation of the main pulmonary trunk was significantly higher in group 1 than group 2 (P = 0.04) and mean attenuations in other vessels were not significant different. SNR and CNR were not significantly different between the groups. The proportion of diagnostic image qualities for chest CT angiography (CTA) was similar between the groups (93.5 vs. 93.9 %). In coronary CTA, group 1 showed a higher proportion of diagnostic image qualities than group 2 (100 vs. 87.9 %). The use of wide-volume mode of 320-detector CT reduces the overall effective radiation dose and results in similar attenuation and image quality for TROCT as compared with the helical mode.
Transcatheter hepatic arterial chemoembolization using emulsions composed of anticancer agents and gelatin sponges (GS) has been an efficient and safe palliative treatment for inoperable hepatocellular carcinoma (HCC). We employed catheter-mediated left hepatic arterial embolization (CHAE) to increase transduction efficiency of adenoviral vector in canine hepatocytes. The emulsion was prepared by mixing pieces of GSP and adenoviral vectors expressing recombinant b-galactosidase (Ad.LacZ) or human hepatocyte growth factor (Ad.hHGF). After the left hepatic artery was catheterized under angiography, CHAE with Ad.LacZ or Ad.hHGF was performed. Livers were removed and stained for LacZ activity on day 7. The expression pattern of LacZ staining was either scarce or patchy around the central hilum of the hepatic artery, or was homogeneously distributed in whole lobes, depending on whether large or small pieces of GSP were used. Hematological and serum biochemical changes during CHAE exhibited only a few effects. The chronological measurement of serum HGF concentration showed that the duration of transgene expression was greater after CHAE with Ad.hHGF. A similar pattern of transgene expression was observed in a rat model after hepatic arterial embolization with differential doses of Ad.hHGF soaked in GSP. These results suggest that hepatic arterial embolization by transcatheter mediated infusion with a mixture of adenovirus-GSP could be used for human HCC.
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