AIM: To investigate the combined effect of etoposide and radiation on CT26 colorectal adenocarcinoma implanted into BALB/c mice.METHODS: We evaluated the radiosensitizing effect of etoposide on CT26 colorectal adenoca...AIM: To investigate the combined effect of etoposide and radiation on CT26 colorectal adenocarcinoma implanted into BALB/c mice.METHODS: We evaluated the radiosensitizing effect of etoposide on CT26 colorectal adenocarcinoma in a syngeneic animal model. BALB/c mice were subcutaneously implanted with CT26 cells and divided into four groups:control (intra-peritoneal salinex2) group, etoposide (5 mg/kgintra-peritoneallyx2) group, radiation therapy (RT 5 Gyx2fractions) group, and combination therapy with etoposide (5 mg/kg intra-peritoneally 1 h before radiation) group.RESULTS: Tumor growth was significantly inhibited by RT and combination therapy. The effect of combination therapy was better than that of RT. No significant changes were noted in body weight, plasma alanine aminotransferase,or creatinine in any group. The leukocyte count significantly but transiently decreased in the RT and combination therapy groups, but not in the etoposide and control groups. There was no skin change or hair loss in the RT and combination therapy groups.CONCLUSION: Etoposide can sensitize CT26 colorectal adenocarcinoma in BALB/c mice to RT without significant toxicity.展开更多
Treatment with etoposide (VP-16) has been associated with translocation of the mixed lineage leukaemia (MLL) gene seen in treatment-related acute myeloid leukaemia (t-AML). Among the different partner genes, AF9 is th...Treatment with etoposide (VP-16) has been associated with translocation of the mixed lineage leukaemia (MLL) gene seen in treatment-related acute myeloid leukaemia (t-AML). Among the different partner genes, AF9 is the most common partner gene of MLL. AF9 shares similar structural element with the MLL gene. Various mechanisms of translocation have been proposed for the MLL gene, including apoptosis, particularly the apoptotic nuclease. In the current study, we show that VP-16 induced cleavage of the AF9 gene in both leukaemic cells and cultured normal blood cell. All the breakpoints were mapped within the BCR1 of the AF9 gene. AF9 cleavages in leukaemic cells were abolished by pre-treatment with caspase inhibitor (Z-DEVD-FMK), suggesting the involvement of caspase-activated DNase (CAD). The absence of AF9 cleavage in K562 cells further supported the involvement of apoptosis. However, AF9 cleavages in cultured normal blood cell were not eliminated by caspase inhibitor. The possible role of CAD and other apoptotic nucleases/effectors that could be involved in AF9 translocation are discussed.展开更多
基金Supported by the Grant, No. MMH 9352 from Mackay Memorial Hospital, Taipei, Taiwan, China
文摘AIM: To investigate the combined effect of etoposide and radiation on CT26 colorectal adenocarcinoma implanted into BALB/c mice.METHODS: We evaluated the radiosensitizing effect of etoposide on CT26 colorectal adenocarcinoma in a syngeneic animal model. BALB/c mice were subcutaneously implanted with CT26 cells and divided into four groups:control (intra-peritoneal salinex2) group, etoposide (5 mg/kgintra-peritoneallyx2) group, radiation therapy (RT 5 Gyx2fractions) group, and combination therapy with etoposide (5 mg/kg intra-peritoneally 1 h before radiation) group.RESULTS: Tumor growth was significantly inhibited by RT and combination therapy. The effect of combination therapy was better than that of RT. No significant changes were noted in body weight, plasma alanine aminotransferase,or creatinine in any group. The leukocyte count significantly but transiently decreased in the RT and combination therapy groups, but not in the etoposide and control groups. There was no skin change or hair loss in the RT and combination therapy groups.CONCLUSION: Etoposide can sensitize CT26 colorectal adenocarcinoma in BALB/c mice to RT without significant toxicity.
文摘Treatment with etoposide (VP-16) has been associated with translocation of the mixed lineage leukaemia (MLL) gene seen in treatment-related acute myeloid leukaemia (t-AML). Among the different partner genes, AF9 is the most common partner gene of MLL. AF9 shares similar structural element with the MLL gene. Various mechanisms of translocation have been proposed for the MLL gene, including apoptosis, particularly the apoptotic nuclease. In the current study, we show that VP-16 induced cleavage of the AF9 gene in both leukaemic cells and cultured normal blood cell. All the breakpoints were mapped within the BCR1 of the AF9 gene. AF9 cleavages in leukaemic cells were abolished by pre-treatment with caspase inhibitor (Z-DEVD-FMK), suggesting the involvement of caspase-activated DNase (CAD). The absence of AF9 cleavage in K562 cells further supported the involvement of apoptosis. However, AF9 cleavages in cultured normal blood cell were not eliminated by caspase inhibitor. The possible role of CAD and other apoptotic nucleases/effectors that could be involved in AF9 translocation are discussed.
