金丝桃苷对耐长春新碱结肠癌HCT8/VCR细胞耐药逆转作用

目的:探讨金丝桃苷对耐长春新碱结肠癌HCT8/VCR细胞的耐药逆转作用及其可能的作用机制。方法:分别以不同质量浓度(2.5~80 mg·L-1)的金丝桃苷及不同质量浓度(1.25~40 mg·L-1)的长春新碱作用于体外培养的HCT8和HCT8/VCR细胞48 h,采用噻唑蓝(MTT)比色法测定细胞生长抑制率,计算各组细胞金丝桃苷和长春新碱的半数抑制浓度(IC50)及金丝桃苷抑制率为5%的药物浓度;采用非毒性剂量金丝桃苷分别与不同质量浓度(1.25~40 mg·L-1)的长春新碱联合作用HCT8/VCR细胞,检测长春新碱的IC50,计算逆转倍数;采用流式细胞仪检测细胞凋亡率及线粒体膜电位变化,比色法检测含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)-3,Caspase-9蛋白活性的变化。结果:金丝桃苷非细胞毒性剂量为0.82mg·L-1。0.82 mg·L-1金丝桃苷可使长春新碱对HCT8/VCR细胞的IC50从65.97 mg·L-1下降至9.94 mg·L-1,逆转倍数为6.63;与单独用长春新碱组比较,长春新碱与金丝桃苷联合用药组细胞凋亡率,Caspase-3,Caspase-9蛋白活性均显著提高(P0.01)。线粒体膜电位检测发现,与单独用长春新碱组及金丝桃苷组比较,长春新碱与金丝桃苷联合用药组低荧光强度相对细胞数所占比率显著提高(P0.01)。结论:长春新碱与金丝桃苷联合应用后可增强Caspase-3,Caspase-9蛋白活性,降低线粒体膜电位,提高HCT8/VCR细胞的凋亡率,从而产生耐药逆转作用。     

长春新碱对HL—60细胞肌醇磷脂代谢和增殖的影响

长春新碱作用于~3H—肌醇标记的人早幼粒白血病HL—60细胞.发现~3H—PI急剧减少,在检测的1～120min内.仅为对照组的38.55％～61.01％.而~3H—PIP、~3H—PIP_2含量无明显变化.表明长春新碱不影响HL—60细胞PI激酶和PIP激酶活性。却迅速且持久地促进PI的水解;同时检测到长春新碱明显抑制细胞增殖和DNA合成.提示长春新碱抑制HL—60细胞增殖与干扰肌醇磷脂代谢有关。     

Accumulation of vincristine and doxorubicin in malignant lymphocytes with different immunophenotypes

Cellular accumulation of vincristine (VCR) and doxorubicin (DOX) was studied in 15 patients with low-grade B-cell malignancies. Their leukemic lymphocytes were isolated and the effect of verapamil on drug uptake was studied. The immunophenotype was characterized using anti-IgM, -IgD, -B 1, monoclonal antibodies. The more that cells bound the IgD or B1 antibodies, the more vincristine and doxorubicin did they accumulate. The fewer the cells that bound IgM antibodies, the more drug did they accumulate.     

Autoradiographic investigation of proliferative responses in rat incisor pulp after vincristine administration

0.7 mg/kg VCR was given to nine rats in three experimental groups. Twenty-three hours after VCR injection the animals were injected with ³H-thymidine. The animals were sacrificed 24, 48 and 72 h after the VCR injection, and by comparison with nine control animals similarly injected with sodium chloride solution and nucleotide, it was shown that VCR causes a delayed migration of pulp cells from the proliferative pool and a small but distinct inhibition of the incisal growth of the incisors. The growth inhibition corresponded to the normal growth over a 24-h period in nou-VCR-injected animals.     

Combination chemotherapy with cyclophosphamide,vincristine, procarbazine,and prednisone (COPP) in children with brain tumors

Summary The chemotherapeutic combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) was used to treat 15 children with recurrent central nervous system tumors and seven children with newly diagnosed brainstem tumors. In patients with recurrent tumors, marginal activity was seen in various histologic types. COPP chemotherapy was clearly ineffective in patients with brainstem tumors. Toxicity consisted of mild to moderate myelosuppression and neurotoxicity.     

An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil,methotrexate, and prednisone in advanced breast cancer

Summary A multi-institutional randomized clinical trial was carried out to evaluate the effect of vincristine (V) added to cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) for the treatment of metastatic breast cancer. There were 427 patients entered into the study and randomly assigned to one of the two treatments, i.e. the five drug therapy CMFPV or the four drug therapy CMFP. The differences in patient survival and tumor response between the two treatment groups were not statistically significant. The data were also analyzed using multivariate procedures to determine those factors ascertained at entry into the study which were predictors of survival or predictors of response to therapy. The one factor that predicted both response and survival was performance status. An additional important predictor of survival was sites of metastatic involvement. Other significant predictors of response were menopausal age, BUN, and hematocrit.Deceased, February, 1985     

Vincristine's effect on dentinogenesis in rat incisor

Abstract – Vincristine was administered to 60 rats in four groups in doses of 0,1, 0,3, 0,5 and 0.7mg/kg. Histomorphologic investigation of the dentin and odontoblasts in the maxillary incisors after 1, 2 and 3 weeks revealed a moderate to severe disturbance of dentin production in some parts of the incisors. In some of the affected areas the effect seemed to be reversible in that normal-appearing dentin was found pulpal to the dentinal derangements after 2 and 3 weeks. The distribution and severity of the lesions were similar to those previously observed 3 days after injection of the same doses of vincristine.     

Leukemias induced by ethylnitrosourea in Wistar rats: incidence and chemotherapy.

After application of 15 mg/kg ethylnitrosourea (ENU) weekly for 15 weeks to 200 male Wistar rats, 76 developed acute leukemias, 15 developed chronic myeloid leukemias and 39 had malignomas in other organs. The weekly application of 75 mg/kg ENU to another group of 200 male Wistar rats for 3 weeks caused 57 acute leukemias, 6 chronic myeloid leukemias and 47 malignomas in other organs. From 112 “autochthonous” acute leukemias which were treated with a combination of vincristine, adriamycin and cytosine arabinoside (ADOA), 67 (60%) achieved a complete remission with a median survival time of 64 days (range 25–173). The survival time of this group was significantly increased compared to untreated controls (α = 0.01). Forty-five rats (40%) with acute leukemia died during the first week after start of therapy, or therapy had to be discontinued. The failure of treatment in this group was attributed to the poor general condition of the animals whose platelet counts and hemoglobin values were low, due to late diagnosis.The “autochthonous” acute leukemias demonstrated some parallels with human acute leukemia. Their use in experimental chemotherapy is discussed.