Arsenic Trioxide (ATO) is widely acknowledged as the treatment of choice for Acute Promyelocytic Leukemia (APL). It is a “two-sided” drug since it can induce differentiation or kill APL and other tumor cells accordi...Arsenic Trioxide (ATO) is widely acknowledged as the treatment of choice for Acute Promyelocytic Leukemia (APL). It is a “two-sided” drug since it can induce differentiation or kill APL and other tumor cells according to the dosage. Part of the cytotoxic effects of ATO on APL cells is due to its pro-oxidant activity, a characteristic which ATO shares with a number of other compounds, including high doses of ascorbate (ASC). In a comparative investigation on the cytotoxic effects of both ATO and ASC on HL60 (APL) cell lines, in Vitro, we have been able to confirm the known cytotoxic effects of ATO, but, more importantly, we have demonstrated that ASC is significantly more effective than ATO, in killing these cancer cells in Vitro, when the concentrations are maintained within the millimolar (mM) range, i.e. the range of plasma concentrations at which ASC induces oxidative damage to tumor cells. Since these plasma levels can be reached only by the intravenous administration of high doses of ASC, we propose that intravenous high doses of ASC may represent a potentially revolutionary new approach in the management of APL.展开更多
目的研究白血病相关基因对T细胞急性淋巴细胞白血病(T-ALL)耐药性的影响。方法对38例成人初治T细胞急性淋巴细胞白血病患者通过高通量测序技术检测54种白血病相关基因,将突变率最高基因与81种常用化疗药物在不同浓度下的敏感性相对比,...目的研究白血病相关基因对T细胞急性淋巴细胞白血病(T-ALL)耐药性的影响。方法对38例成人初治T细胞急性淋巴细胞白血病患者通过高通量测序技术检测54种白血病相关基因,将突变率最高基因与81种常用化疗药物在不同浓度下的敏感性相对比,探讨该基因与药物敏感性之间的相关性,同时与实际临床疗效相比较,并研究该基因的临床意义。结果在54种白血病相关性基因中,NOTCH1基因突变率最高,38例患者中18例发生NOTCH1突变,突变组对0.37、1.1、3.3 μmol/L地塞米松药物耐药性高于非突变组( P <0.05),突变组血小板水平低于非突变组( P <0.05),但NOTCH1突变与性别、年龄、白细胞计数、骨髓原始细胞数、血红蛋白水平、LDH水平无相关性( P >0.05)。结论 NOTCH1突变可引起地塞米松耐药,可能为预后不佳指标。展开更多
文摘Arsenic Trioxide (ATO) is widely acknowledged as the treatment of choice for Acute Promyelocytic Leukemia (APL). It is a “two-sided” drug since it can induce differentiation or kill APL and other tumor cells according to the dosage. Part of the cytotoxic effects of ATO on APL cells is due to its pro-oxidant activity, a characteristic which ATO shares with a number of other compounds, including high doses of ascorbate (ASC). In a comparative investigation on the cytotoxic effects of both ATO and ASC on HL60 (APL) cell lines, in Vitro, we have been able to confirm the known cytotoxic effects of ATO, but, more importantly, we have demonstrated that ASC is significantly more effective than ATO, in killing these cancer cells in Vitro, when the concentrations are maintained within the millimolar (mM) range, i.e. the range of plasma concentrations at which ASC induces oxidative damage to tumor cells. Since these plasma levels can be reached only by the intravenous administration of high doses of ASC, we propose that intravenous high doses of ASC may represent a potentially revolutionary new approach in the management of APL.
文摘目的研究白血病相关基因对T细胞急性淋巴细胞白血病(T-ALL)耐药性的影响。方法对38例成人初治T细胞急性淋巴细胞白血病患者通过高通量测序技术检测54种白血病相关基因,将突变率最高基因与81种常用化疗药物在不同浓度下的敏感性相对比,探讨该基因与药物敏感性之间的相关性,同时与实际临床疗效相比较,并研究该基因的临床意义。结果在54种白血病相关性基因中,NOTCH1基因突变率最高,38例患者中18例发生NOTCH1突变,突变组对0.37、1.1、3.3 μmol/L地塞米松药物耐药性高于非突变组( P <0.05),突变组血小板水平低于非突变组( P <0.05),但NOTCH1突变与性别、年龄、白细胞计数、骨髓原始细胞数、血红蛋白水平、LDH水平无相关性( P >0.05)。结论 NOTCH1突变可引起地塞米松耐药,可能为预后不佳指标。
