Objective: To study the effects of extremely low frequency (ELF) magnetic field with fixed parameters on human liver cancer cells (SK-HEP-1) at different aspects. Methods: SK-HEP-1 cells were exposed to 50Hz, 20mT magnetic field during the whole culture process, and then proliferation activity, growth kinetics, metabolic profile and cell cycle were analyzed. Results: 50Hz, 20mT magnetic field inhibits the growth and metabolism of SK-HEP-1 cells, and hampers their mitotic division. Conclusion: 50Hz, 20mT magnetic field could be a potential therapy in the treatment of human malignant tumors.

BACKGROUND: Magnetic field can affect the growth and division of cancer cells both in vivo and in vitro, however, the effects on apoptosis of human liver cancer cells induced by magnetic field is still unclear.OBJECTIVE: To explore the inducing effect of extremely low fre quency (ELF) magnetic field on apoptosis of human liver cancer cell SK-HEP- 1.JESIGN: An open experiment with cells as the observational subjects.SETTING: Institute of Biotechnology, Shanghai Jiaotong University.MATERIALS: The experiment was carried out at the Institute of Biotechnology, Shanghai Jiaotong University from September 2004 to January 2005. The subject was human liver cancer cell line SK-HEP-1, purchased from cell bank of Chinese Academy of Science, Shanghai.METHODS: SK-HEP-1 cells were inoculated to T-flasks at the density of 2.0×107 cells L-1, and cultivated in the DMEM containing 0.1 volume fraction of heat-inactivated fetal bovine serum and 2 mmol/L L-glutamine. Exposure groups were exposed to 50 Hz, 20 mT magnetic field and the control groups were run concurrently under the same conditions with the exposed cultures but in a separate incubator which was free of magnetic field during 8-day culture process. The apoptosis of SK-HEP-1 cells were defined by DNA ladder assay, Hoechst 33258 staining and AO/EB staining respectively on day 8.MAIN OUTCOME MEASURES: ① DNA fragmentation pattern formation. ② The abnormal nucleus formation. ③ The percentage of apoptotic cells.RESULTS: ① Detection of internucleosomal DNA fragmentation by DNA ladder assay: After 8-day ELF magnetic field exposure, DNA fragmentation pattern was detected by DNA ladder assay, which was not observed in control groups (free of exposure). ② Fluorescence microscopy analysis of apoptosis by Hoechst 33258 staining: Hoechst 33258 staining was used to investigate the changes in the nucleus of cells, and many apoptotic bodies containing nuclear fragments were found in ELF magnetic field exposed cells, but just about none in untreated cells. At the same time, cytoplasmic shrinkage was observed in cells cultured under the exposure. And in some cells, even the cell membrane was unable to keep intact. ③ Fluorescence microscopy analysis of cell apoptosis by acridine orange/ethidium bromide (AO/EB) double staining: After ELF magnetic field exposure, the percentage of viable cells in exposure groups (9.2%) was rather low compared with the control groups (91.8%), and was accompanied with a high apoptotic rate (72.3%), while only 4.2% in control group. A large number of apoptotic cells were at the early stage of apoptosis. The rate of apoptotic cells (18.5%)after treated by magnetic field was higher than that of control group (4%). With the AO/EB double staining, control cells appeared to be round,intact and bright green while some of the exposed cells exhibited irregular cell morphology and condensed nucleus.CONCLUSION: Apoptosis of human liver cancer cell SK-HEP-1 could be induced by 50 Hz, 20 mT magnetic field in vitro.

OBJECTIVETo explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.

METHODSA single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.

RESULTSAll patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.

CONCLUSIONSAA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Anemia, Aplastic ; drug therapy ; Benzoates ; therapeutic use ; Blood Transfusion ; China ; Ferritins ; blood ; Humans ; Iron ; blood ; Iron Chelating Agents ; therapeutic use ; Iron Overload ; drug therapy ; Liver ; Prospective Studies ; Triazoles ; therapeutic use