BACKGROUND: This study was designed to examine how glutathione, one of the nucleophilic sulfur compounds, effects the cisplatin cellular toxicity in the non-small cell lung cancer cell lines and normal lung epithel ial cell line. METHODS: Three cultured cell lines, the lung adenocarcinoma cell(NCL-H23), the lung squamous carcinoma cell (SK-MES-1) and the normal lung epithelial cell(L-132) line were exposed to various concentrations of cisplation with or without glutathione. The relative viability was estimated as a means of measuring the cisplatin cellular toxicity using the MTT method. RESULTS: In NCL-23, the response to cisplatin was sensitive but glutathione markedly increased the relative survival of the tumor cells by removing the antitumor effect of cisplatin. In both SK-MES-1 and L-132, the responses to cisplatin were less sensitive, and the chemoprotective effect of glutathione compared to an equal cisplatin dose was signigicantly higher in L-132 than in SK-MES-1(p<0.05). CONCLUSION: The protective effects of glutathione on cisplatin-induced cellular toxicity is more signigicant in normal lung epithelial cells than in squamous carcinoma cells.
Adenocarcinoma ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Cell Line* ; Cells, Cultured ; Cisplatin ; Epithelial Cells ; Glutathione* ; Lung ; Sulfur Compounds

PURPOSE: 99mTc-sestamibi (MIBI) and 99mTc-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of 99mTc-MIBI and 99mTc-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. MATERIALS AND METHODS: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. RESULTS: RT-PCR, western blot analysis of the cells and immunochemical staining revealed selective expression of Pgp and MRP for HCT15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p< 0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. CONCLUSION: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.
Animals ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; Cell Line ; Colorectal Neoplasms ; Cyclosporine ; Drug Resistance ; Drug Resistance, Multiple* ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Multidrug Resistance-Associated Proteins* ; P-Glycoprotein* ; Radioactivity ; Technetium Tc 99m Sestamibi

BACKGROUND: Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years. METHODS: The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study. RESULTS: The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1+/-1.9 g/dL, mean corpuscular volume was 93.4+/-11.6 fL, and mean number of reticulocytes was 19,700/mm3. The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%). CONCLUSION: The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.
Anemia ; Anemia, Diamond-Blackfan ; Aortic Coarctation ; Bone Marrow ; Congenital Abnormalities ; Diamond ; Erythrocyte Indices ; Heart Septal Defects, Ventricular ; Hemoglobins ; Hospitals, University ; Humans ; Incidence ; Korea ; Male ; Medical Records ; Registries ; Reticulocytes ; Retrospective Studies ; Steroids ; Strabismus ; Thumb ; Transplants