AIM:To evaluate the clinical efficacy and safety of epirubicin,cisplatin,and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma(HCC).METHODS:From April 2009 to June 2012,31 ...AIM:To evaluate the clinical efficacy and safety of epirubicin,cisplatin,and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma(HCC).METHODS:From April 2009 to June 2012,31 patients who were diagnosed with metastatic and progressive HCC after sorafenib treatment were retrospectively reviewed.Patients were treated with the combination of epirubicin(50 mg/m2Ⅳ;day 1),cisplatin(60 mg/m2Ⅳ;day 1),and 5-FU(1000 mg/m2Ⅳ;day 1-3)[Epirubicin,cisplatin,5-FU combination(ECF)],repeated every 4 wk.RESULTS:The overall response rate was 12.9%.Patients who responded to ECF chemotherapy showed a longer overall survival(OS)and time to progression(TTP)relative to those in the non-responder group(OS:20.4 mo vs 4.9 mo,P<0.001,TTP:9.4 mo vs 2.2 mo,P<0.001).Patients with a stable primary liver mass also exhibited a longer OS and TTP relative to those with progressive disease(OS:13.4 mo vs 5.3 mo,P=0.003;TTP:9.4 mo vs 2.3 mo,P=0.003).The most common hematologic toxicity was thrombocytopenia(87.2%),and the incidence of grade 3-4 neutropenia was 53.9%.Age older than 60,a stable primary mass,and a good response to chemotherapy were prognostic factors for OS and TTP.CONCLUSION:This combination cytotoxic chemotherapy can serve as another treatment option after sorafenib failure for the subset of patients with advanced metastatic HCC.展开更多
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 c...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.展开更多
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 pat...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.展开更多
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. Howev...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.展开更多
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 resis...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.展开更多
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 pat...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.展开更多
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 can...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.展开更多
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 a...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.展开更多
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 ...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.展开更多
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-resis...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.展开更多
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 i...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.展开更多
目的:探讨术前血清叉头框蛋白O1(Fork head box protein O1,FoxO1)和脂肪酸转运蛋白4(fatty acid-binding protein 4,FABP4)与非肌层浸润性膀胱癌(Non-muscle invasive bladder cancer,NMIBC)患者灌注治疗疗效的关系。方法:选取2021年1...目的:探讨术前血清叉头框蛋白O1(Fork head box protein O1,FoxO1)和脂肪酸转运蛋白4(fatty acid-binding protein 4,FABP4)与非肌层浸润性膀胱癌(Non-muscle invasive bladder cancer,NMIBC)患者灌注治疗疗效的关系。方法:选取2021年1月至2022年10月期间本院收治的68例NMIBC患者作为研究对象。所有患者进行经尿道膀胱肿瘤切除术(Transurethral resection of bladder tumor,TURBT)治疗,患者术后给予表柔比星膀胱灌注。随访12 m,根据最终的病理结果,将患者分为复发组和未复发组。检测对比两组术前血清FOXO1水平和FABP4水平。分析术前血清FABP4水平与TURBT术后膀胱灌注疗效的相关性及诊断价值。结果:68例患者TURBT术后给予表柔比星膀胱灌注,复发率22.1%。复发组术前血清FOXO1水平与未复发组无明显差异(P>0.05);复发组术前血清FABP4水平显著高于未复发组(P<0.05)。以术前血清FABP4水平预测TURBT术后给予表柔比星膀胱灌注治疗后复发的AUC=0.7052。结论:术前血清高FABP4水平提示TURBT术后给予表柔比星膀胱灌注治疗易复发,其用来预测表柔比星膀胱灌注治疗效果有较高价值。展开更多
Small cell lung cancer(SCLC)is frequently disseminated and has a dismal prognosis with survival times of approximately two years.This cancer responds well to initial chemotherapy but recurs within a short time as a gl...Small cell lung cancer(SCLC)is frequently disseminated and has a dismal prognosis with survival times of approximately two years.This cancer responds well to initial chemotherapy but recurs within a short time as a globally chemoresistant tumor.Circulating tumor cells(CTCs)are held responsible for metastasis,the extremely high numbers of these cells in advanced SCLC allowed us to establish several permanent CTC cell lines.These CTCs are distinguished by the spontaneous formation of large spheroids,termed tumorospheres,in regular tissue culture.These contain quiescent and hypoxic cells in their interior and are associated with high chemoresistance compared to single cell cultures.Nine CTC lines were compared for their expression of 84 proteins associated with cancer either as single cells or in the form of tumorospheres in Western blot arrays.With the exception of the UHGc5 line,all other CTC lines express EpCAM and lack a complete EpCAM-negative,vimentin-positive epithelial-mesenchymal transition(EMT)phenotype.Upon formation of tumorospheres the expression of EpCAM,that mediates cell-cell adhesion is markedly upregulated.Proteins such as E-Cadherin,p27 KIP1,Progranulin,BXclx,Galectin-3,and Survivin showed variable changes for the distinct CTC cell lines.In conclusion,EpCAM presents the most critical marker for individual SCLC CTCs and the assembly of highly chemoresistant tumorospheres.展开更多
文摘AIM:To evaluate the clinical efficacy and safety of epirubicin,cisplatin,and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma(HCC).METHODS:From April 2009 to June 2012,31 patients who were diagnosed with metastatic and progressive HCC after sorafenib treatment were retrospectively reviewed.Patients were treated with the combination of epirubicin(50 mg/m2Ⅳ;day 1),cisplatin(60 mg/m2Ⅳ;day 1),and 5-FU(1000 mg/m2Ⅳ;day 1-3)[Epirubicin,cisplatin,5-FU combination(ECF)],repeated every 4 wk.RESULTS:The overall response rate was 12.9%.Patients who responded to ECF chemotherapy showed a longer overall survival(OS)and time to progression(TTP)relative to those in the non-responder group(OS:20.4 mo vs 4.9 mo,P<0.001,TTP:9.4 mo vs 2.2 mo,P<0.001).Patients with a stable primary liver mass also exhibited a longer OS and TTP relative to those with progressive disease(OS:13.4 mo vs 5.3 mo,P=0.003;TTP:9.4 mo vs 2.3 mo,P=0.003).The most common hematologic toxicity was thrombocytopenia(87.2%),and the incidence of grade 3-4 neutropenia was 53.9%.Age older than 60,a stable primary mass,and a good response to chemotherapy were prognostic factors for OS and TTP.CONCLUSION:This combination cytotoxic chemotherapy can serve as another treatment option after sorafenib failure for the subset of patients with advanced metastatic HCC.
基金Supported by National Natural Science Foundation of China,No.81560345
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China (Grant No.81373334)
文摘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.
基金grants from the National Natural Science Foundation of China(No.81072152 and No.81770283)Natural Science Foundation of Hubei Province(No.2015CFA027)+1 种基金Research Foundation of Health and Family Planning Commission of Hubei Province(No.WJ2015MA010 and No.WJ2017M249)Clinical Medical Research Center of Peritoneal Cancer of Wuhan (No.2015060911020462).
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘目的:探讨术前血清叉头框蛋白O1(Fork head box protein O1,FoxO1)和脂肪酸转运蛋白4(fatty acid-binding protein 4,FABP4)与非肌层浸润性膀胱癌(Non-muscle invasive bladder cancer,NMIBC)患者灌注治疗疗效的关系。方法:选取2021年1月至2022年10月期间本院收治的68例NMIBC患者作为研究对象。所有患者进行经尿道膀胱肿瘤切除术(Transurethral resection of bladder tumor,TURBT)治疗,患者术后给予表柔比星膀胱灌注。随访12 m,根据最终的病理结果,将患者分为复发组和未复发组。检测对比两组术前血清FOXO1水平和FABP4水平。分析术前血清FABP4水平与TURBT术后膀胱灌注疗效的相关性及诊断价值。结果:68例患者TURBT术后给予表柔比星膀胱灌注,复发率22.1%。复发组术前血清FOXO1水平与未复发组无明显差异(P>0.05);复发组术前血清FABP4水平显著高于未复发组(P<0.05)。以术前血清FABP4水平预测TURBT术后给予表柔比星膀胱灌注治疗后复发的AUC=0.7052。结论:术前血清高FABP4水平提示TURBT术后给予表柔比星膀胱灌注治疗易复发,其用来预测表柔比星膀胱灌注治疗效果有较高价值。
基金partially funded by the“Medical Scientific Fund of the Mayor of the City of Vienna”,Grant Number 21040 to Dr.C.Lang.
文摘Small cell lung cancer(SCLC)is frequently disseminated and has a dismal prognosis with survival times of approximately two years.This cancer responds well to initial chemotherapy but recurs within a short time as a globally chemoresistant tumor.Circulating tumor cells(CTCs)are held responsible for metastasis,the extremely high numbers of these cells in advanced SCLC allowed us to establish several permanent CTC cell lines.These CTCs are distinguished by the spontaneous formation of large spheroids,termed tumorospheres,in regular tissue culture.These contain quiescent and hypoxic cells in their interior and are associated with high chemoresistance compared to single cell cultures.Nine CTC lines were compared for their expression of 84 proteins associated with cancer either as single cells or in the form of tumorospheres in Western blot arrays.With the exception of the UHGc5 line,all other CTC lines express EpCAM and lack a complete EpCAM-negative,vimentin-positive epithelial-mesenchymal transition(EMT)phenotype.Upon formation of tumorospheres the expression of EpCAM,that mediates cell-cell adhesion is markedly upregulated.Proteins such as E-Cadherin,p27 KIP1,Progranulin,BXclx,Galectin-3,and Survivin showed variable changes for the distinct CTC cell lines.In conclusion,EpCAM presents the most critical marker for individual SCLC CTCs and the assembly of highly chemoresistant tumorospheres.