Epirubicin,Cisplatin,5-FU combination chemotherapy in sorafenib-refractory metastatic hepatocellular carcinoma

AIM: To evaluate the clinical efficacy and safety of epirubicin, cisplatin, and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma (HCC).

Docetaxel, cisplatin, and 5-fluorouracil compared with epirubicin,cisplatin, and 5-fluorouracil regimen for advanced gastric cancer:A systematic review and meta-analysis

BACKGROUND As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil(DCF) and epirubicin, cisplatin, and 5-fluorouracil(ECF) regimens are commonly used in clinical practice, but there is still controversy about which is better.AIM To compare the efficacy and safety of DCF and ECF regimens by conducting this meta-analysis.METHODS Computer searches in PubMed, EMBASE, Ovid MEDLINE, Science Direct, Web of Science, The Cochrane Library and Scopus were performed to find the clinical studies of all comparisons between DCF and ECF regimens. We used progression-free survival(PFS), overall survival(OS), objective response rate(ORR), disease control rate(DCR), and adverse effects(AEs) as endpoints for analysis.RESULTS Our meta-analysis included seven qualified studies involving a total of 598 patients. The pooled hazard ratios between the DCF and ECF groups were comparable in PFS(95%CI: 0.58-1.46, P = 0.73), OS(95%CI: 0.65-1.10, P = 0.21),and total AEs(95%CI: 0.93-1.29, P = 0.30). The DCF group was significantly better than the ECF group in terms of ORR(95%CI: 1.13-1.75, P = 0.002) and DCR(95%CI: 1.03-1.41, P = 0.02). However, the incidence rate of grade 3-4 AEs was also greater in the DCF group than in the ECF group(95%CI: 1.16-1.88, P = 0.002),especially for neutropenia and febrile neutropenia.CONCLUSION With better ORR and DCR values, the DCF regimen seems to be more suitable for advanced gastric cancer than the ECF regimen. However, the higher rate of AEs in the DCF group still needs to be noticed.

Unfavorable Pathological Complete Response Rate of Neoadjuvant Chemotherapy Epirubicin plus Taxanes for Locally Advanced Triple-negative Breast Cancer

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer （TNBC）. Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m^2 plus paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response （pCR）, which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival （RFS） and overall survival （OS） were secondary endpoints. Thirty-nine （90.7%） patients were at clinical stages II B-IIIC. Thirty-seven （86%） completed 4-6 cycles of preop- erative chemotherapy, and objective response rate （ORR） was 81.4% （35/43）. Forty-two patients un- derwent radical surgery subsequently. The pCR rate was 14.3% （6/42）. The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting （88.4%, 38/43） and neutropenia （88.4%）. After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally ad- vanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

The effect of monosialylganglioside mix modifying the PEGylated liposomal epirubicin on the accelerated blood clearance phenomenon

PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. However, PEG-modified liposomes can induce accelerated blood clearance(ABC) upon repeated administration, and the extent of ABC phenomenon on the cytotoxic drugs-containing PEGylated liposomes is related to the dose of the cytotoxic drugs.In this study, EPI served as a model cytotoxic drug, a hydrophilic surfactant molecule,monosialylganglioside(GM1) was chosen and modified on the liposomes together with PEG.It was shown that upon mixed modification, when GM1 contents reached 10% or 15% mol,the ABC phenomenon of the PEGylated liposomal EPI significantly reduced. We also found that GM1 played an important role in abrogating the ABC phenomenon in both the induction phase and the effectuation phase. The results suggested that GM1 incorporation unfortunately did not avoid occurrence of ABC phenomenon completely, but GM1 modification on PEGylated liposomes may provide a significant improvement in clinical practice of PEGylated liposomes. Further study must be necessary.

DJ-1 Alters Epirubicin-induced Apoptosis via Modulating Epirubicin-activated Autophagy in Human Gastric Cancer Cells

Epirubicin,which is a conventional chemotherapeutic drug for gastric cancer,has innate and adaptive chemoresistance.Recent studies revealed that epirubicin could induce autophagy as a defensive mechanism in drug resistance of mammary carcinoma.Another study implied that D J-1 may be a chemoresistance-related gene.But the association between D J-1 and drug resistance of epirubicin in gastric cancer is still ambiguous.In the present report,we explored whether and how D J-1 conduced to epirubicin-induced apoptosis in gastric cancer.Epirubicin dose-dependently increased the expression of DJ-1 and induced autophagy.Knockdown of DJ-1 notably enhanced epirubicin-induced cell apoptosis,whereas overexpression of DJ-1 attenuated epirubicin-induced cell apoptosis.Further studies revealed that down-regulation of DJ-1 modulated epirubicin-activated autophagy which augmented epirubicin-induced apoptosis.In conclusion,our results validated that DJ-1 reduced epirubicin-induced apoptosis in gastric cancer cells via modulating epirubicin-activated autophagy.

Evaluation of Epirubicin-induced Cardiotoxicity by Two-dimensional Strain Echocardiography in Breast Cancer Patients

The value of two-dimensional strain echocardiography for assessing left ventricular regional systolic function in breast cancer patients who were treated with epirubicin was evaluated. A total of 116 breast cancer patients were divided into 3 groups： Thirty-eight patients in group A were given epirubicin （Epi） of 120-340 mg/m^2, 42 patients in group B received epimbicin of≥ 360 mg/m^2, and 36 patients after surging without chemotherapy served as the control group C. High frame rate two-dimensional images were recorded from apical long-axis view, four-chamber view, two-chamber view of left ventricle. Peak systolic strain of left ventricular subendocardial myocardium was measured using two-dimensional strain software. The conventional echocardiographic parameters were also obtained. Conventional echocardiography showed there was no significant changes in conventional echocardiographic parameters among the three groups （P〉0.05）. Two-dimensional strain echocardiography revealed that the peak systolic strain of left ventricular subendocardial myocardium in group A was reduced in some segments as compared with the controls （P〈0.05）. The peak systolic strain of left ventricular subendocardial myocardium in group B was reduced significantly as com- pared with group C （P〈0.05）, but that was reduced in group B just in some of the segments as compared with group A （P〈0.05）. It was concluded that two-dimensional strain echocardiography could early and sensitively display the effects of epirubicin-induced cardiotoxicity on the systolic function of left ventricular subendocardial myocardium, and early monitor the epirubicin-induced cardiotoxicity.

Quality of Life of Patients with Metastatic Breast Cancer Treated with Epirubicin and Docetaxel

This phase II study assessed the clinical response and short-term quality of life of patients receiving first-line chemotherapy with epirubicin-docetaxel combination for metastatic breast cancer. Thirty-one breast cancer patients were treated with epirubicin (75 mg/m2 for 15 minutes) followed one hour later by a one-hour infusion of docetaxel (75 mg/m2) q3w. EORTC QLQ-C30 and EORTC QLQ-BR23 forms were filled in at baseline, and at the second and eighth cycle of chemotherapy. The combination of epirubicin and docetaxel provided a high degree of clinical benefit. Clinical response was observed in 17 patients (55%), including five (16%) complete responses and 12 (39%) partial responses. Of responding and stable patients 23 (74%) maintained the same status for at least six months (clinical benefit). The mean survival time was 40.8 months. During the treatment the emotional functioning improved and the concerns about the future were relieved. Some aspects of quality of life were impaired, with slightly decreased physical and cognitive functioning, distress related to body image and hair loss, and adverse effects of chemotherapy. Overall, the global quality of life was maintained.

Epirubicin治疗曾化疗与未化疗晚期乳腺癌的疗效对比

Epirubicin单药治疗晚期乳腺癌,按照用过化疗与未用过化疗的病人分为两组。两组病人均按每次剂量递增的方法,50mg/M^2,60mg/M^2,70mg/M^2～80mg/M^2静脉注射,每3周1次。结果,未曾化疗的病人达PR的4/9例(44.4％),MR3/9(33.3％),NC2/9(22％)。曾用化疗的病人达CR1/11例(9％),MR2/11例(18％),NC1例,PD7例。Epi-Dx的心肌毒性与骨髓毒性较低,无1例发生急性充血性心力衰竭。本实验表明未曾化疗的病人比曾经化疗的病人疗效较高。

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

Purpose: Discover the anti-neoplastic efficacy of epirubicin-(C13-imino)-[anti-HER2/neu] against chemotherapeutic- resistant SKBr-3 mammary carcinoma and delineate the capacity of selenium to enhance it’s cytotoxic anti-neoplastic potency. Methods: In molar excess, EMCH was combined with epirubicin to create a covalent epirubicin-(C13-imino)-EMCH-maleimide intermediate with sulfhydryl-reactive properties. Monoclonal immunoglobulin selective for HER2/neu was then thiolated with 2-iminothiolane at the terminal ε-amine group of lysine residues. The sulfhydryl-reactive epirubicin-(C13-imino)-EMCH intermediate was then combined with thiolated anti-HER2/neu monoclonal immunoglobulin. Western-blot analysis was utilized to characterize the molecular weight profiles while binding of epirubicin-(C13-imino)-[anti-HER2/neu] to membrane receptors was determined by cell-ELISA utilizing populations of SKBr-3 mammary carcinoma that highly over-expresses HER2/neu complexes. Anti-neoplastic potency of epirubicin-(C13-imino)-[anti-HER2/ neu] between the epirubicin-equivalent concentrations of 10–12 M and 10–7 M was determined by vitality staining analysis with and without the presence of selenium (5 μM). Results: Epiribucin-(C13-imino)-[anti-HER2/neu] between epirubicin-equivalent concentrations of 10–8 M to 10–7 M consistently evoked higher anti-neoplastic potency than “free” non- conjugated epirubicin which corresponded with previous investigations utilizing epirubicin-(C3-amide)-[anti-HER2/neu] and epirubicin-(C3-amide)-[anti-EGFR]. Selenium at 5 mM consistently enhanced the cytotoxic anti-neoplastic potency of epirubicin-(C13-imino)-[anti-HER2/neu] at epirubicin equivalent concentrations (10–12 to 10–7 M). Conclusions: Epirubicin-(C13-imino)-[anti-HER2/neu] is more potent than epirubicin against chemotherapeutic-resistant SKBr-3 mammary carcinoma and selenium enhances epirubicin-(C13-imino)-[anti-HER2/neu] potency. The methodology applied for synthesizing epirubicin-(C13-imino)-[anti-HER2/neu] is relatively time convenient and has low instrumentation requirements.

Epirubicin-gold nanoparticles suppress hepatocellular carcinoma xenograft growth in nude mice

We sought to investigate the effects of epirubicin-nanogold compounds （EPI-AuNP） on hepatocellular carcinoma xenograft growth in nude mice. EPI-AuNP was prepared and hepatoma xenograft model was established in nude mice. The mice were then randomly divided into four groups： the control group with injection of saline, the AuNP treatment group, the EPI treatment group and the EPI-AuNP treatment group. After two weeks, the hepatoma weight and volume of the xenografts were assessed. Our transmission electron microscopy revealed that epirubicin- gold nanoparticles caused significantly more structural changes of hepatocellular carcinoma cells HepG2. The tumor weight in the Epi-AuNP treatment group （0.80 ± 0.11 g） was significantly lower than that of the control group （2.48±0.15 g）, the AuNP treatment group （1.67±0.17 g）, and the EPI treatment group （1.39±0.10 g） （P〈0.01）. Furthermore, the tumor volume of mice in the EPI-AuNP treatment group （0.27 ± 0.06 cm3） was significantly smal- ler than that of the control group （2.23 ± 0.34 cm3）, the AuNP treatment group （1.21 ± 0.25 cm3） and the EPI treat- ment group （0.81 ± 0.11 cm3） （P〈0.01）. In conclusion, epirubicin-nanogold compounds （EPI-AuNP） have significant inhibitory effects on the growth of hepatocellular carcinoma cells in vivo.

The cardiotoxicity and long-term efficacy of different doses of epirubicin in the adjuvant treatment of breast cancer patients: A case control study

Abstract Objective： The aim of the study was to observe the cardiac toxicity caused by different doses of epirubicin in the adjuvant treatment of breast cancer and to evaluate the long-term efficacy. Methods： The 180 cases of breast cancer patients received epirubicin based adjuvant chemotherapy. The patients were randomly assigned to high-dosage group （90 rag/m^2）, medium-dosage group （70 mg/m^2） and low-dosage group （50 rag/m^2）, the primary endpoint was cardiac toxicity. The secondary outcomes were the 5-year overall survival （OS） and 5-year disease-free survival （DFS）. Results： During chemo- therapy, the clinical symptoms such as palpitation, dyspnea and paroxysmal nocturnal dyspnea occurred in 6 patients with the high-dosage group, 4 patients with the medium-dosage group and 3 patients with the low-dosage group. The number of patients who had changed in electrocardiogram （ECG） was 7, 5 and 4 in three groups, respectively. The echocardiographic showed each group had only one case with LVEF 〈 50%, there was no significantly difference （P 〉 0.05）. In the three groups, the 5-year DFS rates were 73.3% （44/60） in high-dose group, 53.3% （32/60） in medium-dose group and 41.6% （25/60） in low dose group. The 5-year OS rates were 85.0% （51/60）, 68.3% （41/60） and 58.3% （35/60） in three groups, respectively. The differences were statistically significant （P 〈 0.05）. Conclusion： The high-dose epirubicin in adjuvant chemotherapy with CEF （cyclophosphamide, epirubicin and fluorouracil） regimen could improve the 5-year OS rate and 5-year DFS rate on patients of breast cancer. The cardiotoxicity was mild-moderate and well tolerated.

Randomized Trial Comparing Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF) Regimen with Rotational CMFEV Regimen (E=Epirubicin, V=Vincristine) as Adjuvant Chemotherapy in Moderate Risk Operable Breast Carcinoma

Objectives: The CMFEV (cyclophosphamide, methotrexate, 5-fluorouracil, epirubicin, vincristine) regimen is an innovative schedule, designed by our Group, aimed at administering five partially or totally no cross-resistant cytotoxic agents in breast carcinoma. It was randomly compared to CMF (cyclophosphamide, methotrexate, 5-fluorouracil) as primary treatment in operable disease and demonstrated a short-term significant increase in clinical complete response rate and a long-term significant locoregional relapse-free survival in premenopausal patients. So, it seemed worth comparing this regimen with CMF as adjuvant chemotherapy in moderate risk operable breast carcinoma. Methods: Four hundred and eighty-nine patients with stage I or II moderate risk breast carcinoma were randomized to receive CMF or CMFEV regimen for 6 cycles after surgery. Main end points were overall survival (OS), invasive disease-free survival (IDFS) and recurrence-free interval (RFI), as estimated by Kaplan-Meier analyses and log-rank tests. Results: At a median observation time of 7.3 years (range 5.4 months-10.3 years), no significant differences in OS and IDFS were observed between the two arms. Deaths from breast carcinoma were more frequent with CMF (58.5%) than with CMFEV regimen (41.7%) as well as recurrences from breast carcinoma (58.8% with CMF and 41.2% with CMFEV). These differences were not statistically significant. Conclusion: CMFEV appears more effective than CMF in preventing recurrences from primary disease in patients with moderate risk stage I-II breast carcinoma. The lack of statistical significance of the observed differences was probably due to the limited number of patients enrolled which rendered the study underpowdered.

A retrospective clinical study of safety and efficacy of vinorelbine/epirubicin/fluorouracil(NEF) regimen as a postoperative chemotherapy for breast cancer

Objective： We aimed to investigate the safety and efficiency of vinorelbine/epirubidn/fluorouracil （NEF） regimen as adjuvant chemotherapy for breast cancer. Methods： From 2005 to 2008, 227 female breast cancer patients were treated with the NEF regimen： vinorelbine 25 mg/m^2 iv on days 1 and 8; epirubicin 60 mg/m2 iv gtt on day 1; 5-Fu 500 mg/m2 iv gtt on day 1. Chemotherapy was repeated every 21-28 days for a total of 6 cycles. Results： The major side effects were neutrope- nia and gastrointestinal syndrome, with a 5-year survival rate of 85.4%, Conclusion： NEF regimen is safe and guarantees a high survival rate which could be recommended as a adjuvant chemotherapy regimen for breast cancer,

Effect of the tea polyphenol combined with epirubicin on the apoptosis, autophagy and invasive growth of bladder cancer cells

Objective: To study the effect of the tea polyphenol combined with epirubicin on the apoptosis, autophagy and invasive growth of bladder cancer cells. Methods: T24 bladder cancer cell lines were cultured and divided into three groups, TP+EPI group were treated with 100 μmol/L tea polyphenol combined with 5 μmol/L epirubicin, EPI group were treated with 5 μmol/L epirubicin and control group were treated with drug-free RPMI medium. The mRNA expression of apoptosis, autophagy and invasion genes was measured after 24 h of treatment. Results: DAB2IP, PTEN, LC3 and Beclin1 mRNA expression in TP+EPI group and EPI group were significantly higher than those in control group while Rce1, YAP, DEK, p62, KPNA2, GRP78, Fra-1, SPOCK1 and CX43 mRNA expression were significantly lower than those in control group;DAB2IP, PTEN and p62 mRNA expression in TP+EPI group were significantly higher than those in EPI group while Rce1, YAP, DEK, LC3, Beclin1, KPNA2, GRP78, Fra-1, SPOCK1 and CX43 mRNA expression were significantly lower than those in EPI group. Conclusion:Tea polyphenol combined with epirubicin can promote the apoptosis and inhibit the autophagy and invasion of bladder cancer cells.

Evidence-based pharmacoeconomic research of pirarubicin and epirubicin as prophylaxis for recurrence in patients with superficial bladder tumors by bladder instillation after transurethral resection of a bladder tumor

In the present study, we aimed to evaluate the efficiency and cost ofpirarubicin （THP） and epirubicin （EPI） as prophylaxis for recurrence in patients with superficial bladder tumors by bladder instillation after transurethral resection of a bladder tumor （TUR-BT）. Standardized evaluation was performed by analyzing research papers. Moreover, expert opinions, studies and cost data were combined to evaluate cost of THP and EPI. With systematic review and expert opinions, we confirmed that THP and EPI were not statistically different when they were used as prophylaxis for recurrence in patients with superficial bladder tumors by bladder instillation after TUR-BT. Moreover, the cost evaluation of THP and EPI needs to be separately discussed according to original/generic drug. The original drug THP had more cost advantages than EPI, while generic EPI had more cost advantages than THP.

表柔比星、紫杉醇化疗辅助胃癌根治术患者血清HSP90α、CYFR211水平变化及预后影响因素分析

目的分析表柔比星联合紫杉醇化疗的胃癌根治术患者血清HSP90α、CYFR211水平及预后影响因素。方法选择胃癌根治术的患者96例,均采用表柔比星联合紫杉醇经动脉介入化疗。比较治疗前、治疗6周后、治疗12周后患者血清HSP90α、CYFR211水平。对患者随访2年,统计患者无进展生存时间(PFS)和总生存时间(OS),根据实体肿瘤WHO客观评价标准对患者预后进行评估,分为预后不良组和预后良好组,并通过单因素分析和多因素logistic回归分析影响胃癌根治术患者预后的危险因素。结果治疗6周后,2组患者血清HSP90α、CYFR211水平较治疗前低(P<0.05),治疗12周后,2组患者血清HSP90α、CYFR211水平较治疗前及治疗6周后低(P<0.05)。患者6个月、1年、2年无进展生存率分别为58.3%、30.2%、20.2%,6个月、1年、2年总生存率分别为81.2%、63.5%、32.6%,中位PFS和OS分别为10个月、16个月。单因素分析显示:胃癌根治术患者的预后与性别、体质指数、手术出血量、手术方式、术后是否出现严重不良反应、胃癌发生部位无关(P>0.05),而与年龄、肿瘤直径、手术时间、胃切除范围、TNM分期、肿瘤分化程度有关(P<0.05);多因素分析显示,年龄、肿瘤直径、胃切除范围、手术时间、TNM分期、肿瘤分化程度是影响胃癌根治术患者预后不良的独立危险因素(P<0.05)。结论表柔比星联合紫杉醇经动脉介入化疗治疗胃癌根治术患者,可以降低血清HSP90α、CYFR211水平,疗效尚可。年龄、肿瘤直径、胃切除范围、手术时间、TNM分期、肿瘤分化程度是胃癌根治术患者预后的独立影响因素。

表柔比星联合奥沙利铂经导管动脉栓塞化疗治疗中晚期原发性肝癌患者的临床疗效

目的目的探讨表柔比星联合奥沙利铂经导管动脉栓塞化疗(TACE)治疗中晚期原发性肝癌患者的临床疗效。方法方法根据治疗方法的不同将96例中晚期原发性肝癌患者分为对照组(n=43)和观察组(n=53),对照组患者采取奥沙利铂TACE治疗,观察组患者采取表柔比星联合奥沙利铂TACE治疗。比较两组患者的临床疗效、肿瘤标志物[血管内皮生长因子(VEGF)、甲胎蛋白(AFP)]水平、肝功能指标[丙氨酸转氨酶(ALT)、白蛋白(ALB)、总胆红素(TBIL)]及不良反应发生情况。结果结果观察组患者的总有效率高于对照组,差异有统计学意义(P﹤0.05)。治疗后,两组患者VEGF、AFP水平均低于本组治疗前,观察组患者VEGF、AFP水平均低于对照组,差异均有统计学意义(P﹤0.05)。治疗后,两组患者ALT、TBIL水平均低于本组治疗前,ALB水平均高于本组治疗前,观察组患者ALT、TBIL水平均低于对照组,ALB水平高于对照组,差异均有统计学意义(P﹤0.05)。两组患者的不良反应总发生率比较,差异无统计学意义(P﹥0.05)。结论结论表柔比星联合奥沙利铂TACE治疗中晚期原发性肝癌患者,可提高临床疗效,降低肿瘤标志物水平,改善肝功能,且不会增加不良反应。

特异性下调尿路上皮癌细胞HER-2表达增强表柔比星抗肿瘤效应的实验研究

目的:观察在尿路上皮癌细胞内特异性下调人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)表达对表柔比星(epirubicin,EPI)抗肿瘤效应的影响。方法:对比正常尿路上皮细胞系SV-HUC-1与3种尿路上皮癌细胞系T24、SW780、TCCSUP的HER-2蛋白表达差异,并筛选出其中HER-2表达较高的尿路上皮癌细胞T24与TCCSUP;设计针对HER-2基因的小干扰RNA-siHER-2,将其导入T24和TCCSUP细胞,观察siHER-2特异性下调T24和TCCSUP细胞HER-2表达的效率;随后将siHER-2和EPI共同导入T24和TCCSUP细胞,采用流式细胞术检测各组细胞凋亡水平的差异;并采用Western Blot检测各组细胞PI3K/AKT/mTOR凋亡信号通路相关蛋白表达水平。结果:3种尿路上皮癌细胞的HER-2表达均明显高于正常尿路上皮细胞(P<0.01);siHER-2可明显下调T24和TCCSUP细胞内HER-2表达量(P<0.01);siHER-2与EPI联合应用,可显著提高T24和TCCSUP细胞的凋亡率(P<0.001);同时两种细胞内p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR明显下调(P<0.001)。结论:特异性下调尿路上皮癌细胞内HER-2表达可有效增强EPI的抗肿瘤效应,可作为尿路上皮癌治疗的一种新型策略。

表柔比星联合环磷酰胺致2级间质性肺病1例

目的:为肿瘤患者安全使用表柔比星联合环磷酰胺治疗(即EC方案)提供参考。方法:临床药师参与1例罕见EC方案致CTCAE(common terminology criteria for adverse events,不良事件通用术语标准)评价为2级间质性肺病患者的救治,并检索PubMed、Elsevier Science Direct、中国知网、万方等数据库查阅表柔比星、环磷酰胺致肺病案例,分析患者不良反应特点及治疗经过。结果:临床药师参考文献资料,建议医师暂停患者全身化疗,并经呼吸科专家会诊,给予泼尼松治疗,患者间质性肺病缓解。结论:临床药师应对恶性肿瘤患者加强药学监护,及时发现药物导致的不良反应,并参考文献资料,提出合理化建议,保障患者用药安全、有效。

Development of an HPLC-UV method for the simultaneous determination of epirubicin,amlodipine and dequalinium in anti-resistant liposomes

Novel anti-resistant liposomes have been developed to overcome intrinsic resistance in leukemia.Anticancer agent epirubicin and apoptotic inducer amlodipine were encapsulated into the liposome aqueous core,and the surface of the liposome was modified using dequalinium.The objective of the present study was to establish a high performance liquid chromatography （HPLC） method for the determination of epirubicin,amlodipine and dequalinium in the liposomes.Analysis was performed on an ODS column with an isocratic elution at ambient temperature.Mobile phase was consisted of acetonitrile,0.02 M NaH_2PO_4 and triethylamine（34：66：0.3,v/v/v,pH 4.0）.The detection wavelength was set at 240 nm and the flow rate was 1.0 mL/min.The results showed that the calibration curves of epirubicin,amlodipine and dequalinium were linear in the range of（1-50）μg/mL（r^2= 0.9999）, respectively.The mean recoveries of epirubicin,amlodipine,and dequalinium were in the range of 95.86%-97.52%,97.17%-98.92% and 98.04%-101.13%,respectively.The contents of epirubicin,amlodipine and dequalinium in the liposomes were in the range of（564.2-606.1）μg/mL,（641.0-704.0）μg/mL,and（816.0-898.0）μg/mL,respectively.The encapsulation efficiencies of epirubicin and amlodipine were around 90%,and the modification rate of dequalinium was approximate 70μg/μmol lipids.The proposed HPLC method was simple and accurate for the simultaneous determination of epirubicin,amlodipine and dequalinium in newly developed anti-resistant liposomes.