Apoptotic resistance can either be desirable or undesirable, depending on the conditions. In cancer chemotherapy, it is critical that tumor cells are selectively and effectively killed while leaving normal cells undamaged. Since acquisition of apoptotic resistance appears to be a common occurrence during malignant transformation, elucidating the mechanisms underlying apoptotic resistance is an area of intense study. Previous studies have revealed that metallothionein (MT) can protect cells from apoptosis induced by oxidative stress and metals. In the present study, we tested the hypothesis that the presence of MT may somehow modulate apoptosis. Our results revealed a strong linear negative correlation between basal MT levels and etoposide-induced apoptosis in the human tumor cell lines PLC/PRF/5, H460, and HepG2 (r = -0.991). In HepG2 cells, 24 h pretreatment with cadmium resulted in concentration-dependent increases in MT levels and marked decreases in etoposide-induced apoptosis. Zinc pretreatment also resulted in increased MT synthesis and decreased etoposide-induced apoptosis. More importantly, induced MT levels were negatively correlated with sensitivity to etoposide-induced apoptosis (r = -0.965). These suggest that MT may play a role in regulating apoptosis and that modulating MT expression may provide a strategy for altering cellular resistance to chemotherapeutic compounds.

The type, incidence, and severity of complications of balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric varices should be precisely estimated. Complications were evaluated in 38 patients who had fundic gastric varices and 43 B-RTO procedures during injection of ethanolamine oleate (phase 1), within 4 h after injection (phase 2), 24 h after injection (phase 3), and from 24 h to 10 days after injection (phase 4). Endoscopic evaluation at 8 weeks showed resolution of gastric varices in 35 of 38 patients (92%) and smaller varices in the remaining three (8%). B-RTO caused transient hypertension in 35% of patients, hemoglobinuria in 49%, and fever in 33% during phases 1, 2, and 3, respectively. Pleural effusion, pulmonary infarction, ascites, gastric ulcers with unique appearance, localized mosaic-like change of gastric mucosa, and hemorrhagic portal hypertensive gastropathy were noted in phase 4. There were no fatalities. Lactate dehydrogenase, aspartate aminotransferase, and bilirubin increased on day 1. Each datum was retrieved within 7 days. The severity of lactate dehydrogenase elevation correlated significantly with the volume of infused ethanolamine oleate. Thus, B-RTO is a safe and effective management of fundic varices. However, short-term hemodynamic change after B-RTO may cause gastric mucosal damage. Pulmonary infarction and pleural effusion are potential complications.

Emergency B-RTO is an effective treatment for the prevention of rebleeding from ruptured gastric varices.

Metallothionein (MT) often reduces the adverse effects of cadmium (Cd), but how it may alter Cd-induced apoptosis is unclear. The goal of this study was to define the role of MT in Cd-induced apoptosis using cell lines with widely varying sensitivity to Cd. Effects of Cd on growth of human hepatocellular carcinoma cell lines (HepG2 and PLC/PRF/5) were investigated and compared with Chang cells. These cells were cultured with 0, 5, 10, 20, 40, 80, and 120 microM of Cd for 3, 6, 12, and 24 h. Significant cytolethality was observed in HepG2 and PLC/PRF/5 cells in a time- and concentration-dependent manner, with LC(50) values of 24 microM and 13 microM, respectively. However, Chang cells were much less sensitive to Cd-induced cytotoxicity (LC(50), 64 microM). Apoptotic cell death occurring at cytolethal concentrations was demonstrated in all cell lines by DNA fragmentation on agarose gel electrophoresis or by ELISA. When MT was measured, there was a highly significant negative linear correlation between the basal cellular MT concentration or Cd-induced MT and the rate of apoptosis induced by Cd in these cell lines. Treating HepG2 cells with zinc (Zn) made the relatively sensitive HepG2 cell line resistant to Cd-induced apoptosis, likely due to Zn-induced MT. In fact, there was also a significant negative linear correlation between the amount of Zn-induced MT in HepG2 cells and the rate of Cd-induced apoptosis. These findings revealed that basal or induced MT perturbs Cd-induced apoptotic cell death in various cell lines, and a strong negative correlation exists between cellular MT content and the rate of apoptosis induced by Cd.