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Desferoxamine 이 시험관내 인체 간암세포 성장에 미치는 영향
송시영(Si Young Song),김원호(Won Ho Kim),전미연(Mi Yun Chon),한광협(Kwang Hyub Han),정재복(Jae Bock Chung),전재윤(Chae Yoon Chon),문영명(Young Myung Moon),강진경(Jin Kyung Kang),박인서(In Suh Park),최흥재(Heung Jai Choi),윤정구(Jung 대한내과학회 1994 대한내과학회지 Vol.47 No.3
N/A Objectives: It has been known that excessive iron promote the growth of cancer cells aad suggested that iron oversupply in cancer patients may enhance tumor growth and adversely affect cancer therapy and that desferoxamine (DFO) as a iron chelating agent may have a place in anticancer agents, which acts as a potent inhibitor of DNA synthesis via inhibition of the ribonucleotide reductase. However there have been no reports on the combined effect of DFO with other chemotherapeutics in vitro, This study was done to answer the questions: Does DFO inhibit the growth of cultured hepatoma cells? and Does the combination of DFO and chemotherapeutic agents have a synergistic effect on inhibition of tumor growth? Methods: Using PLC/PRF/5 and Hep G2 cells as hepatoma cells and normal diploid cells of WI-38 as control, the MTT assay was performed for evaluation of the cytotoxicity and an isobologram method to analyze the combined effects of DFO and other chemotherapeutic agents. Results: 1) The hepatoma cells grew faster in an iron-enriched medium than in the medium without additional iron supplementation but the normal diploid cells of WI-38 did not. 2) The 50% inhibitory concentrations (IC50) on PLC/ PRF/5 and Hep 62 cells were 75.1 and 29.1 ㎍/ml, respectively. But the growth of WI-38 was not inhibited below 74.4% with even 200 ㎍/ml of DFO. 3) On both hepatoma cells, the growth inhibitory effects of DFO were reversed with simultaneous administration of stoichiometric doses of ferric citrate. 4) Adriamycin (ADR), 5-fluorouracil (5-FU) and cisplatin (DDP) inhibited the growth of all 3 cell lines, but larger doses were required to inhibit the WI-38 to obtain the same effect. 5) When DFO was combined with chemotherapeutic agents, a marked synergistic effect was observed with the combination of DFO and 5-FU on PLC/PRF/5 cells. The synergistic effect was also noted in Hep G2 cells with all three combinations of DFO-ADR, DFO-5-FU and DFO-DDP. Conclusion: Iron oversupply may enhance the hepatoma growth and this should be taken into consideration treating patients with hepatoma. And the antitumor effect of DFO and its synergistic effect with other chemotherapeutic agents may suggest that iron chelator like the DFO may be a useful treatment for patients with hepatoma in conjuction with other anticancer drugs.
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