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Hepatocellular carcinoma (HCC) is one of the most severe sequelae of chronic liver disease. The only potentially curative therapeutic options are surgical resection and orthotopic liver transplantation. In most HCC patients, however, at clinical presentation the tumors are unresectable because of multicentricity or poor hepatic functional reserve due to pre-existing cirrhosis or not transplantable because of too advanced tumor stage or severe co-morbidity. In clinical practice, therefore, percutaneous ethanol injection (PEI) and transarterial chemoembolization (TACE) are widely used non-surgical therapeutic strategies. We prospectively analyzed the clinical factors determining the prognosis of 132 inoperable HCC patients and assessed the feasibility, therapeutic efficacy and safety of PEI, TACE and a combination thereof. Mean age of patients was 64 years; 95% of patients had liver cirrhosis and 39% were Okuda stage I, 48% stage II and 13% stage III. Fifteen patients were treated by PEI (group 1), 33 by TACE (group 2), 39 by TACE and PEI (group 3) and 45 received best supportive care (group 4). Survival correlated with the Child-Pugh class of liver cirrhosis and the Okuda stage of HCC. Favorable prognostic parameters were alpha-fetoprotein (AFP) levels <100 ng/ml and absence of portal vein thrombosis. Median survival time was 18 months in group 1 [interquartile range (IQR) 10–19], 8 months in group 2 (IQR 5–15), 25 months in group 3 (IQR 13–36) and 2 months in group 4 (IQR 1–9). Multivariate analysis revealed that patients treated with a combination of TACE and PEI have a significantly better survival than patients receiving either PEI or TACE only (p = 0.001). Patients with inoperable HCCs treated by the combination of TACE and PEI have a clear survival benefit. A favorable outcome can be expected in patients with compensated cirrhosis, a low Okuda stage, a baseline AFP level <100 ng/ml and absence of portal vein thrombosis. Int. J. Cancer (Pred. Oncol.) 79:601–605, 1998. © 1998 Wiley-Liss, Inc.

Calreticulin binds Zn 2+with the relatively high affinity/low capacity. To determine the location of the Zn 2+binding site in calreticulin different domains of the protein were expressed in E. coli, using the glutathione S-transferase fusion protein system, and their Zn 2+-dependent interaction with Zn 2+-IDA-agarose were determined. Three distinct domains were used in this study: the N + P-domain (the first 290 residues); the N-domain (residues 1–182) and the proline-rich P-domain (residues 180–273). The N + P-domain bound to the Zn 2+-IDA-agarose and were eluted with an increasing concentration of imidazole. The N-domain also bound 65Zn 2+as measured by the overlay method. The P-domain did not interact with the Zn 2+-IDA-agarose and it did not bind any detectable amount of Zn 2+. Chemical modification of calreticulin with diethyl pyrocarbonate indicated that five out of seven histidines were protected in the presence of Zn 2+but they were modified by diethyl pyrocarbonate in the absence of Zn 2+suggesting that these residues may be involved in Zn 2+binding to calreticulin. We conclude that Zn 2+binding sites in calreticulin are localized to the N-domain of the protein, region that is not involved in Ca 2+binding to calreticulin.