排序方式: 共有12条查询结果,搜索用时 15 毫秒
1.
目的:探讨环孢素A(CsA)联合α-干扰素(IFN-α)逆转复发难治性急性白血病的临床疗效。方法:彩用免疫组织化学标记链亲和法检测初诊急性白血病的P-糖蛋白表达。将P-糖蛋白阳性者随机分为两组,比较CsA联合IFN-α加化疗组与单用化疗组的疗效。结果:P-糖蛋白的阳性表达率在非难治性急性白血病为10.9%,在难治性急性白血病为66.7%(P〈0.01)。CsA联合IFN-α对逆转难治性急性白血病的多药耐药有一定作用,加逆转剂组缓解率(CR+PR)及完全缓解期高于不加逆剂组(P〈0.05)。结论:CsA联合IFN-α逆转难治性急性白血病安全有效。 相似文献
2.
Deng WJ Yang XQ Liang YJ Chen LM Yan YY Shuai XT Fu LW 《Acta pharmacologica Sinica》2007,28(6):913-920
Aim: FG020326, a novel imidazole derivative, is a potent multidrug-resistance (MDR) modulator in vitro and in vivo. However, FG020326 is insoluble. PEDLLA-FG020326 is a FG020326-1oaded nanoparticle formed with diblock copolymers of poly (ethylene glycol)-block-poly (D,L-lactic acid) (PEG:PDLLA, PEDLLA) that can solubilize FG020326. This work was intended to evaluate the pharmacodynamics of PEDLLA-FG020326 on reversing MDR in vitro and in vivo. Methods: Cytotoxicity was determined by tetrazolium assay. The intracellular accumulation and efflux of doxorubicin (Dox) were detected by fluorescence spectrophotometry. The function of P-glycoprotein was examined by Rhodamine 123 (Rh123) accumu- lation detected by flow cytometry. The KBv200 cell xenograft model was established to investigate the effect of PEDLLA-FG020326 on reversing MDR in vivo. Resdts: PEDLLA-FG020326 and FG020326 exhibited 56.4- and 35.9-fold activity in reversing KBv200 cells to vincristine (VCR) resistance, respectively and 14.98- and 7.64-fold to Dox resistance, respectively. PEDLLA-FG020326 was much stronger than FG020326, resulting in the increase of Dox and Rh123 accumulation and the decrease of intracellular Dox extrusion in KBv200 cells. Importantly, PEDLLA- FG020326 exhibited more powerful activity than FG020326 in enhancing the effect of VCR against KBv200 cell xenografts in nude mice, but did not appear more toxic. Conclusion: The pharmacodynamics of FG020326 was improved by incorporating it into a micellar nanoparticle formed with PEG-block-PDLLA copolymers. 相似文献
3.
4.
目的观察阿霉素在耐药株LoVo/Adr细胞内的摄入及分布特点,探讨其耐药机制。方法采用流式细胞术检测阿霉素在细胞中的摄入;利用荧光显微镜观察阿霉素在细胞内的分布;采用免疫组化法检测P-糖蛋白(P-gp)的表达。结果LoVo/Adr细胞内阿霉素含量显著低于LoVo细胞,且阿霉素在核区分布明显减少,相对在胞质中增多;而在敏感LoVo细胞中,阿霉素集中分布在核区,胞质中很少。加入维拉帕米后,不仅LoVo/Adr细胞对阿霉素的蓄积能力显著增强,而且可使阿霉素在LoVo/Adr细胞中的分布恢复到敏感状态。P-gp染色在LoVo细胞株均为阴性,而耐药株LoVo/Adr细胞膜呈强阳性。结论阿霉素在耐药细胞中不仅摄入减少,而且分布异常,主要与P-gp有关,P-gp是药物耐药的机制之一。 相似文献
5.
BCR-ABL酪氨酸激酶抑制剂靶向治疗慢性粒细胞白血病(chronic myeloid leukemia, CML)能够达到良好的临床效应,然而随着其临床广泛应用,对其产生耐药逐渐增多。CML细胞多药耐药是目前导致化疗失败,缓解率降低,疾病复发的主要原因。本文就CML对BCR-ABL酪氨酸激酶靶向抑制剂耐药的主要机制进行了阐述。 相似文献
6.
Expression of P-glycoprotein and p53 in advanced hepatocellular carcinoma treated by single agent chemotherapy: Clinical correlation 总被引:3,自引:0,他引:3
YUH-YU CHOU ANN-LII CHENG HEY-CHI HSU 《Journal of gastroenterology and hepatology》1997,12(8):569-575
Hepatocellular carcinoma (HCC), a chemoresistant tumour, is the most common fatal cancer in Taiwan. Hepatocellular carcinoma frequently expresses a high level of P-glycoprotein (P-gp), which is a specific phenotype of a multidrug-resistance gene, and harbours mutations of the tumour suppressor gene p53. A modulatory relationship between p53 and P-gp has been reported. In this study, we analysed the expression of P-gp in relation to chemotherapeutic response and p53 protein expression in advanced HCC. Prechemotherapeutic tumour samples were obtained from 25 patients with HCC which had been treated with either etoposide (VP-16) or doxorubicin. P-glycoprotein and p53 in HCC were visualized by immunohistochemical staining using the monoclonal antibodies JSB-1 and DO1, respectively. We investigated the correlation of P-gp expression with chemotherapeutic responses, clinicopathological features and p53 protein expression. In our study, seven cases achieved partial remission, and the remaining 18 cases had a poor response to chemotherapy. Expression of P-gp was observed in 13 tumours (52%). Positive P-gp protein expression was significantly associated with non-responders (8% or 1/13 vs 50% or 6/12, P= 0.03). Thus, P-gp expression inversely correlated with chemotherapeutic response. Expression of p53 protein was seen in 12 cases and did not correlate with chemosensitivity or P-gp expression. In summary, P-gp expression correlates with the chemosensitivity of HCC that has been treated with VP-16 or doxorubicin and p53 mutations do not appear to be a major determinant of P-gp expression in advanced HCC. 相似文献
7.
复发难治性急性白血病多药耐药逆转的临床研究 总被引:1,自引:0,他引:1
目的:探讨环孢素A(CsA)联合α-干扰素(IFN-α)逆转复发难治性急性白血病的临床疗效。方法:彩用免疫组织化学标记链亲和法检测初诊急性白血病的P-糖蛋白表达。将P-糖蛋白阳性者随机分为两组,比较CsA联合IFN-α加化疗组与单用化疗组的疗效。结果:P-糖蛋白的阳性表达率在非难治性急性白血病为10.9%,在难治性急性白血病为66.7%(P<0.01)。CsA联合IFN-α对逆转难治性急性白血病的多药耐药有一定作用,加逆转剂组缓解率(CR+PR)及完全缓解期高于不加逆剂组(P<0.05)。结论:CsA联合IFN-α逆转难治性急性白血病安全有效。 相似文献
8.
9.
以人肝癌细胞SMMC-7721为母细胞株.在体外通过逐渐增加抗癌药丝裂霉素(MMC)浓度以共培养方式建立具有MDR特性的人肝癌细胞株。与母细胞株相比较.该株对MMC的抗药性增加了4.5倍。另外.通过对细胞培养各个阶段的MDRI基因表达情况的观察及用抗P-糖蛋白抗体MRK16证实.所建立的人肝癌细胞抗药株具有稳定性、较高的MDR1基因表达特点。因此.该细胞株的建立.对肝癌化疗的研究提供了一个有用的模型。 相似文献
10.
目的研究和完善乳腺癌细胞多药耐药机制及多药耐药后肿瘤细胞的性质、行为改变。方法分别对野生组(MCF-7)、阿霉素诱导的耐药组(MCF-7/ADM)、撤药60d组(MCF-7/撤药60d)进行细胞学分析,观察细胞增殖速度及群体增殖时间,SP免疫组化法检测细胞表型变化。结果MCF-7/ADM与MCF-7细胞增殖速度无明显差异,撤药组随着撤药时间的延长,细胞的增殖速度加快,群体倍增时间缩短;MCF-7/ADM、MCF-7/撤药60d细胞的分化程度低于MCF-7组;MCF-7/ADM的耐药相关标记蛋白Pgp、LRP、GST-π、HER-2表达较MCF-7明显增加,而雌激素受体(ER)、TOPO-Ⅱ转为阴性表达,孕激素受体(PR)随撤药时间的延长表达逐步减低。结论应用阿霉素诱导的MCF-7具有明显的耐药细胞性状,耐药细胞具有去分化的能力;耐药细胞的遗传和生化特性发生了变化,可用于肿瘤多药耐药机制的研究。 相似文献