PURPOSE: Cellular uptake of 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance (MDR) by p-glycoprotein (Pgp) or multidrug related protein (MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. MATERIALS AND METHODS: Cellular uptakes of Tc-99m MIBI and TF were measured in erythroleukemia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562 (Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto 200 micro M at 1x10 (6) cells/ml at 37degrees C. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. RESULTS: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562 (Adr) cell at a concentration of 100 micro M and the maximal increase at 50 micro M was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over 1 micro M. With a concentration of 200 micro M verapamil, MIBI and TF uptakes in K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with 10 micro M, but were also decreased with verapamil higher than 10 micro M, resulting 40% and 5% of baseline at 50 micro M. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at 200 micro M. CONCLUSION: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.
Blotting, Western ; Breast Neoplasms ; Cell Line ; Drug Resistance, Multiple ; Humans ; K562 Cells ; Leukemia, Erythroblastic, Acute ; MCF-7 Cells ; Ovarian Neoplasms ; P-Glycoprotein ; Radioactivity ; RNA, Messenger ; Technetium Tc 99m Sestamibi ; Verapamil*

BACKGROUNDS: Living-donor liver transplantation (LDLT) has been established as an efficacious option to resolve the shortage of cadaveric donor organs for pediatric recipients. This surgical innovation has significantly reduced the pretransplantation mortality for children, but the crisis of increasing scarcity of donor organs in our hospital has led us to extend LDLT to adult recipients. However, the extension of LDLT from pediatric recipients to adult recipients has been made only with limited success largely because of the inability of a relatively small-size left-lobe graft to meet the metabolic demands of an adult recipient. It has been postulated that a left-lobe graft smaller than 40% of the recipient's standard liver volume will not result in a successful adult-to-adult LDLT in chronic parenchymal liver disease. METHODS: From February 1997 to October 1997, 10 LDLTs, using 9 extended left-lobe grafts and 1 right-lobe graft, were performed on patients with end-stage parenchymal liver diseases (9 cases of B-hepatitis-induced cirrhosis with or without an associated hepatocellular carcinoma and 1 case of alcoholic cirrhosis) at the Department of Surgery, Asan Medical Center. The ratios of the graft to the standard liver volume of the recipients were in the range of 30% to 55%. RESULTS: All grafts showed immediate function, but delayed normalization of the serum total bilirubin was demonstrated in all recipients receiving left-lobe grafts. There were no mortalities and serious complications in donors. Two recipients died of sepsis 21 days and 40 days after transplantation, and 8 recipients (80%) are alive with good liver function at a median follow-up of 5.1 months (range 2~10 months). CONCLUSIONS: The aim of this article is to report our experience with adult-to-adult LDLT shows that a graft size greater than 30% of the recipient's standard liver volume is able to meet the metabolic demands of adult recipients with chronic parenchymal liver disease and that LDLT might open a new donor pool for adult recipients when the supply of cadaveric organs is severely restricted.
Adult ; Alcoholics ; Bilirubin ; Cadaver ; Carcinoma, Hepatocellular ; Child ; Chungcheongnam-do ; Fibrosis ; Follow-Up Studies ; Humans ; Liver Diseases ; Liver Transplantation* ; Liver* ; Living Donors* ; Mortality ; Sepsis ; Tissue Donors ; Transplants