Anaplastic lymphoma kinase (ALK) gene rearrangement and chimeric nucleophosmin (NPM)- ALK fusion oncoprotein were first identified in anaplastic large cell lymphoma (ALCL).LM1 is an ALK-pos. DLBCL cell line expressing the CLTC-ALK oncoprotein.To examine the anti-lymphoma effect of As203 on ALK-pos. DLBCL cells, LM1 cells were treated with varying concentrations of As₂O₃ for 48 h, followed by cell viability assay.To investigate if the downregulation of CLTC-ALK was mediated by proteasomal protein degradation, LM1 cells were pre-treated with the proteasome inhibitor MG-132 prior to As₂O₃ treatment.In conclusion, CLTC-ALK is a therapeutic target of As₂O₃, and As₂O₃ treatment represents a novel therapeutic approach for ALK-pos. DLBCL.Moreover, As₂O₃ targets the ALK moiety of ALK fusion protein, suggesting that As203 may be a potential therapeutic agent for other ALK-pos. malignancies.

2017-10-26·Asian Pacific journal of cancer prevention : APJCP

Evaluation on Efficacy and Safety of Arsenic Trioxide Plus Transcatheter Arterial Chemoembolization Versus Transcatheter Arterial Chemoembolization alone for Unresectable Primary Liver Cancer

Article

作者: Hui-Juan Chen ; Xian-He XIe ; Wan-Zun Lin ; Zi-yuan Liao ; Li-Na Li ; Si-Jing Zhou ; Shui-Mei Luo ; Rui-Fen Shen ; Hai-Tao Yang ; Heng Lin

Currently, some clinical trials of arsenic trioxide (As203) plus transcatheter arterial chemoembolization (TACE) in the treatment of unresectable primary liver cancer (PLC) had been conducted, but the results were controversial. Therefore, we performed a meta-analysis on 14 clinical trials (1076 cases) to evaluate efficacy and safety of As203 plus TACE versus TACE alone for unresectable PLC. The primary end points included objective response rate (ORR), karnofsky performance score (KPS) improvement rate, and 1-year survival rate. The second end points were adverse events consisting of leukopenia, liver dysfunction, nausea/vomiting, fever, myelosuppression and pain. Our study showed that, compared with TACE alone, As203 plus TACE appeared a significant benefit on ORR (RR = 1.32, 95% CI: 1.15,1.50, P < 0.0001), KPS improvement rate (RR = 1.24, 95% CI: 1.03,1.48, P = 0.02) and 1-year survival rate (RR = 1.31, 95% CI: 1.15,1.49, P < 0.0001). Additionally, no remarkable difference of adverse events were observed between two arms: leukopenia (RR = 1.44, 95% CI: 0.90,2.32, P = 0.13), liver dysfunction (RR = 0.96, 95% CI: 0.76,1.21, P = 0.71), nausea/vomiting (RR = 1.10, 95% CI: 0.84,1.44, P = 0.48), fever (RR = 1.15, 95% CI: 0.82,1.61, P = 0.43), myelosuppression (RR = 1.07, 95% CI: 0.74,1.56, P = 0.72) and pain (RR = 0.88, 95% CI: 0.57,1.36, P = 0.57). This study demonstrated that As203 plus TACE produced a favorable efficacy without enhancing adverse events and was a promising combination therapy option for unresectable PLC.

2012-04-30·Asian Pacific Journal of Cancer Prevention

Radiosensitivity Enhancement by Arsenic Trioxide in Conjunction with Hyperthermia in the EC-1 Esophageal Carcinoma Cell Line

Article

作者: Hua, Qin-Liang ; Yang, Qing-Hui ; Li, Si-Qing ; Lu, Ping ; Zhang, Qing-Qin ; Miao, Zhan-Hui ; Liang, Hai-Jun ; Cui, Yan-Hui ; Huo, Xiao-Qing ; Li, Wei-Wei ; Li, Xiao-Rui ; Gu, Jian-Fa

OBJECTIVETo explore the effect on radiosensitivity of arsenic trioxide (As₂0₃) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line.METHODInhibition of EC-1 cell proliferation at different concentrations of As₂0₃ was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of IC₅₀ value and choice of 20% of the IC₅₀ as the experimental drug concentration. Blank control, As₂0₃, hyperthermia, radiotherapy group, As₂0₃ + hyperthermia, As₂0₃ + radiotherapy, hyperthermia + radiotherapy and As₂0₃ + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle.RESULTSAs₂0₃ exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an IC₅₀ of 18.7 μmol/L. After joint therapy of As₂0₃ + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the G₂/M phase, and as the ratio of cells in G₀/G₁ and S phases decreased, cell death became more pronounced.CONCLUSIONAs₂0₃ and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, As₂0₃ and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.

100 项与 AS-203 相关的药物交易

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