Changes of protein expression during tumorosphere formation of small cell lung cancer circulating tumor cells

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.

EP对体外培养CHO细胞存活的影响

本实验观察了不同浓度EP对体外培养中处于静止期及指数生长期 CHO细胞存活的影响。发现1.0μg/ml EP使静止期及指数生长期细胞的种植系数降至对照的49.99％及34.46％;使其存活分数降至0.4999及0.3447。证明EP对体外培养中CHO细胞生长有明显抑制作用。同时发现,随EP浓度的增加,两期细胞的种植系数及存活分数继续下降,以指数期细胞下降尤为显著。说明高浓度EP对指数生长期肿瘤细胞具有更有效的抑瘤作用。此结果可为EP的临床应用提供生物学实验依据。

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).

Isolation and Identification of Cancer Stem Cells from Human Osteosarcom by Serum-free Three-dimensional Culture Combined with Anticancer Drugs

The cancer stem cells(CSCs)from human osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs were isolated and identified.The primary cells derived from human osteosarcoma were digested by trypsin to prepare a single-cell suspension,and mixed homogeneously into 1.2% alginate gel.Single-cell alginate gel was cultured with serum-free DMEM/F12 medium.Epirubicin(0.8μg/mL)was added to the medium to enrich CSCs.After cultured conventionally for 7 to 10 days,most of cells suspended in ...

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.

Relationship between Fas/ FasL expression and apoptosis of colon adenocarcinoma cell lines

INTRODUCTIONFas/ FasL system has been identified as a keymediator of apoptosis in tumor cells[1-4]. Theoccurrence and development of neoplasm are closelyrelated to apoptosis[5-7] Most chemotherapeuticdrugs kill cancer cells mainly by inducingapoptosis[8-14].'

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.

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.

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.

Preparation and Characterization of Superparamagnetic Fe_3O_4/CNTs Nanocomposites Dual-drug Carrier

Fe3O4/carbon nanotubes（Fe3O4/CNTs） nanocomposites were prepared by polylol hightemperature decomposition of the precursor ferric chloride and CNTs in liquid triethylene glycol.After surface modification with hexanediamine,folate was covalently linked to the amine group of magnetic Fe3O4/CNTs nanocomposites.The products were characterized by Fourier-transform infrared spectroscopy,transmission electron microscopy,and vibrating sample magnetometry.Then Fe3O4/CNTs were used as a dual-drug carrier to co-delivery of the hydrophilic drug epirubicin hydrochloride and hydrophobic drug paclitaxel.The results indicated that the Fe3O4/CNTs had a favorable release property for epirubicin and paclitaxel,and thus had potential application in tumor-targeted combination chemotherapy.

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-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.

Effectiveness of taxanes over anthracyclines in neoadjuvant setting:A systematic-review and meta-analysis

BACKGROUND Anthracyclines and taxanes are more active group of chemotherapy regimen.Randomized controlled trials(RCTs) reported variable evidences regarding efficacy of taxanes over anthracyclines for tumor response and survival outcomes. The present study compares the relative efficacy of taxanes over anthracyclines using pathological complete response(pCR), clinical responses,breast-conserving surgeries and survival outcomes in female breast cancer patients by systematic review and meta-analysis of available RCTs.AIM To assess the effectiveness of taxanes over anthracyclines in neoadjuvant setting in terms of tumor response and survival outcomes.METHODS All RCTs assessing efficacy of taxanes over anthracyclines in neoadjuvant setting for management of breast cancer searched through PubMed and Cochrane register of controlled trials on 28 April 2017 and published in English language were considered. Following PRISMA guideline, retrieved records were screened and data were extracted by two independent reviewers. Meta-analysis was performed using fixed effect or random effect method depending on heterogeneity assessed using I^2 statistic. Subgroup meta-analyses on the basis of taxane alone or taxane along with anthracycline in comparison to anthracycline alone were also performed for each considered outcomes.RESULTS A total of 16 RCTs involving 6752 breast cancer patients were found eligible.Taxanes based chemotherapy significantly improved pCR(n = 7, RR = 1.48,95%CI: 1.04-2.12), disease free survival [n = 6, RR = 0.89(0.80-0.99)] and locoregional recurrence free survival [n = 4, RR = 0.74(0.59-0.94)]. Interestingly in subgroup analysis, addition of taxane to anthracyclines showed better effectiveness regarding these survivals over anthracyclines than taxane alone over anthracycline.CONCLUSION Addition of taxanes to anthracyclines based chemotherapy significantly improves pCR, disease free survival and loco-regional recurrence free survival but with no significant impact on breast conservation rates.

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,

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.

参芪十一味颗粒联合EOX方案化疗治疗晚期胃癌27例

最新研究表明胃癌全球每年新发病例100余万例，中国占42％；死亡约80万例，中国占35％，由此可见，中国是胃癌发病率和病死率最高的国家之一，发病率和病死率均是世界平均水平的2倍多。在我国前10位癌症中，胃癌发病率为第2位，病死率为第3位；总体5年生存率＜20％，大部分的初治患者就诊时已为中晚期，已出现局部进展或远处转移［1］，常见患者明显消瘦、贫血、乏力、食欲不振、精神萎糜等症状，生活质量较差。目前，联合化疗是晚期胃癌的主要治疗方法，已有研究［2］证实化疗可以延长晚期胃癌患者的生存期，卡培他滨为近年来用于治疗进展期胃癌的有效药物之一，与奥沙利铂、表柔比星等组成联合治疗方案，并取得了良好的临床效果，但出现中重度胃肠道反应、骨髓毒性及肝肾毒性概率比较高，这些不良反应影响了患者的生活质量及治疗进程。本科于2009年7月-2011年7月采用参芪十一味颗粒联合EOX 方案（表柔比星＋奥沙利铂＋卡培他滨， Epirubicin＋ Oxaliplatin ＋ Capecitabine ）治疗晚期胃癌27例，并与单纯EOX方案化疗27例比较其近期疗效、不良反应和生活质量改善，现报道如下。

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.

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their application.To address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect.In this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into mB4S.After internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP secretion.Meanwhile,diABZI effectively activated the STING pathway.Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.