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Objective:To investigate the correlation of OCA2 gene rs4778137 single nucleotide polymorphism with the prognosis of early breast cancer patients receiving epirubicin-based regimen chemotherapy.Methods:The data of 152 patients with early breast cancer who received epirubicin combined with cyclophosphamide and docetaxel (EC-T regimen) chemotherapy in the First People's Hospital of Ziyang from April 2010 to January 2013 were retrospectively analyzed. OCA2 gene rs4778137 single nucleotide polymorphism of peripheral venous blood before chemotherapy was detected. The follow-up was up to April 2017, recurrence and disease-free survival (DFS) were analyzed. DFS of patients with different rs4778137 locus genotype in patients with different estrogen receptor (ER)/progesterone receptor (PR) expressions, human epithelial factor receptor 2 (HER2) expressions and Ki-67 positive index were analyzed.Results:The median follow-up time was 60 months (28-80 months). There were 2 cases of lost follow-up and 26 cases of recurrence. Among 150 patients with follow-up results, 68 cases (45.33%) of rs4778137 genotype were CC genotype, 47 cases (31.33%) of GC genotype and 35 cases (23.33%) of GG genotype. There were significant differences in N staging, HER2 expression and ER/PR expression among patients with or without recurrence ( χ2 value was 5.79, 6.08 and 6.05; P value was 0.016, 0.014 and 0.014, respectively). The 5-year DFS rate of 150 breast cancer patients was 82.2%, and there was no significant difference in DFS among patients with different rs4778137 locus genotype ( χ2 = 2.35, P = 0.167). Cox regression analysis showed that N staging and ER/PR expression were independent influencing factors of DFS in breast cancer patients (all P < 0.05). Among 71 ER/PR-negative patients, there was a statistically significant difference in DFS of patients with different rs4778137 locus genotype ( χ2 = 6.52, P = 0.030). Among 79 ER/PR-positive patients, 60 HER2-positive patients and 90 HER2-negative patients, 118 cases with Ki-67 positive index >14% and 32 cases with Ki-67 positive index≤14%, there were no statistically significant differences in DFS of patients with different rs4778137 locus genotype (all P > 0.05). Conclusions:The DFS of ER/PR-negative patients with early breast cancer who received epirubicin-based regimen chemotherapy is correlated with OCA2 gene rs4778137 single nucleotide polymorphism. Patients with GG genotype at rs4778137 locus have better prognosis.
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Objective:To compare the efficacy and safety of pegylated liposomal Doxorubicin(PLD)and Epirubicin(EPI)as first-line chemotherapy for diffuse large B-cell lymphoma(DLBCL).Methods:Clinical data of DLBCL patients treated at Zhejiang Cancer Hospital from March 2013 to April 2018 were retrospectively collected.A total of 411 patients who had received first-line chemotherapy were included.Based on age, sex, Ann Arbor staging and other parameters and using the PSM method for 1∶1 matching, 151 patients were assigned into each of the PLD group and the EPI group.Efficacy and adverse events were compared between the PLD group and the EPI group.All patients were followed up for 3 years after treatment to monitor survival.Results:The complete response(CR)rate in the PLD group was 81.5%, and the CR rate in the EPI group was 72.2%.The objective response rate(ORR)of the PLD group was 98%, and the ORR of the EPI group was 96.7%.There was no significant difference in CR rate( χ2=0.478, P=0.489)or ORR between the two groups( χ2=0.007, P=0.934). In the PLD group, myelosuppression occurred in 25 cases(16.6%)and cardiotoxicity-related events in 21 cases(13.9%); in the EPI group, there were 24 cases(15.9%)of myelosuppression and the same number of cases of cardiotoxicity-related events, and there were no significant differences in myelosuppression( χ2=0.018, P=0.895)or cardiotoxicity( χ2=0.174, P=0.677)between the two groups.During the 3-year follow-up, the progression free survival(PFS)rates of the PLD group and the EPI group were 79.1% and 69.6%, respectively, with a statistically significant difference between the two groups( χ2=3.930, P=0.047). Both the PLD group and the EPI group had a 3-year OS rate of 85.2%, with no statistically significant difference between the two groups( χ2=0.402, P=0.538). Conclusions:The 3-year progression-free survival of DLBCL patients with PLD as first-line chemotherapy is significantly better than with EPI, and the 3-year overall survival, short-term efficacy and myelosuppression are comparable to those with EPI.
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ObjectiveTo investigate the effect of hypoxia-inducible factor-1α (HIF-1α) on the stemness and epirubicin sensitivity of hepatoma cells. MethodsHepatoma cells were selected for experiment. HepG2 hepatoma cells transfected with HIF-1α overexpression plasmid were selected as experimental group, and those transfected with pcDNA3.1 empty plasmid were selected as control group; HepG2 cells alone were selected as HepG2 group. Quantitative real-time PCR was used to measure the mRNA expression of HIF-1α; Western blot was used to measure the protein expression of HIF-1α; flow cytometry was used to measure the expression of CD133 on the surface of hepatoma cells. The three groups of cells were treated with epirubicin at different concentrations (0, 6.25, 12.5, 25, and 50 μmol/L) for 24 hours; MTT assay was used to measure cell viability, and flow cytometry was used to measure apoptosis after treatment with epirubicin (50 μmol/L). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the t-test was used for further comparison between two groups. ResultsCompared with the HepG2 group and the control group, the experimental group had a significant increase in the mRNA expression of HIF-1α (both P＜0.001), and Western blot showed high expression of HIF-1α in the experimental group. The percentage of CD133 cells was 0.040%±0.003% in the HepG2 group, 0.030%±0.010% in the control group, and 20.110%±0.600% in the experimental group, and the experimental group had a significantly higher positive rate of CD133+ than the HepG2 group and the control group (both P＜0.001). At an epirubicin concentration of 25 and 50 μmol/L, the HepG2 group and the control group had significantly inhibited cell viability and a significantly lower cell viability than the experimental group (both P＜005). After the treatment with 50 μmol/L epirubicin for 48 hours, the experimental group had a significantly lower cell apoptosis rate than the HepG2 group (67.9%±2.5% vs 93.6%±1.5%, P＜0.001) and the control group (67.9%±2.5% vs 93.0%±1.2%, P＜0001). ConclusionHepG2 cells are successfully transfected with HIF-1α overexpression plasmid, and HIF-1α can increase the percentage of liver cancer stem cells and improve their resistance to epirubicin.
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Objective@#To investigate the influences of cardiovascular risk factors on left ventricular wall motion function in patients treated with epirubicin chemotherapy by layer-specific two-dimensional speckle tracking imaging (2D-STI).@*Methods@#Sixty-four female patients with breast cancer treated with epirubicin and 36 controls from June 2018 to March 2019 in Renmin Hospital of Wuhan University were included. According to the numbers of cardiovascular risk factors, the patients were divided into group A (without cardiovascular risk factors, 31 cases), group B (single cardiovascular risk factor, 20 cases), and group C (multiple cardiovascular risk factors, 13 cases). All patients underwent echocardiography before and after epirubicin respectively. Global longitudinal strain, circumferential strain, radial strain (GLS, GCS, GRS), endocardial and epicardial layers of GLS and GCS (endoGLS, epiGLS, endoGCS, epiGCS) were obtained by EchoPAC software analysis. The differences of GLS, EndoGLS, EpiGLS, GCS, EndoGCS, EpiGCS and GRS before and after chemotheraphy were calculated as ΔGLS, ΔEndoGLS, ΔEpiGLS, ΔGCS, ΔEndoGCS, ΔEpiGCS and ΔGRS.@*Results@#Compared with before chemotherapy, GLS, EndoGLS, EpiGLS, GCS, EndoGCS, EpiGCS and GRS were significantly reduced in group A, B and C after chemotherapy (all P<0.05). ΔEndoGLS and ΔEndoGCS showed an increasing trend in groups A, B and C, with statistical significance (all P<0.05). Correlation analysis showed that after chemotherapy with epirubicin, the numbers of cardiovascular risk factors were significantly correlated with strain parameters, and the correlation coefficient of EndoGLS was relatively higher (r=-0.582, P<0.001).@*Conclusions@#Layer-specific imaging can reliably detect the influences of cardiovascular risk factors on the left ventricular wall motion function in breast cancer patients treated with epirubicin. Parameters reflecting the endocardial longitudinal systolic function are sensitive indicators for the early detectin of myocardial damage and toxicity by epirubicin in patients with multiple cardiovascular risk factors.
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ABSTRACT Propolis is a natural substance, produced by honeybees from the resin of various plants. The purpose of this study was to determine the chemical composition and evaluate the hepatoprotective effect of ethyl acetate extract of propolis from Tigzirt, against the toxicity induced by epirubicin which is a anticancer agent, and belongs to the family of antracyclines. The study included thirty male Wistar albino rats divided into five groups. The rats received the extraction of propolis or the quercetin orally for 15 days. The hepatotoxicity was promoted by injection epirubicin (i.v.) with a cumulative dose of 9 mg/kg. Several biological parameters were measured. Oxidative status was also assessed by evaluating antioxidant enzyme and histological study of some organs. Epirubicin caused oxidative stress by a significant decrease in hepatic antioxidant enzymes (gluthation peroxidase, catalase, superoxide dismutase), increased malondialdehyde and liver parameters (ASAT, ALAT, γGT, ALP) compared to the control. The histological study revealed major damage to the liver. Perturbations in this liver function, antioxidant status and damage to the liver by epirubicin have been repaired by the administration of propolis. Furthermore, epirubicin showed inflammatory effects induced by an increase in TNF-α and PGE2. Pretreatment with propolis to rats restored these inflammatory parameters. The chemical identification of extract of propolis by HPLC/UV shows the presence of polyphenolic compounds and many flavonoids. The propolis extract showed a significant reduction in oxidative damage from oxidative stress and a very important protective effect against epirubicin-induced hepatotoxicity.
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Objective@#We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk.@*Methods@#370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed.@*Results@#370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282).@*Conclusions@#EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.
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Objective To investigate the effects of calcium levofolinate and 5-fluorouracil combined with epirubicin on stress response and vascular endothelial growth factor (VEGF) level in patients with gastric cancer.Methods A total of 160 patients with gastric cancer treated in Huxi Hospital Affiliated to Jining Medical College from April 2016 to March 2018 were selected as research objects.All the patients were divided into two groups according to the random number table method and each group consisted of 80 cases.The control group was treated with epirubicin,while the study group was treated with calcium levofolinate and 5-fluorouracil combined with epirubicin.The clinical efficacy and adverse reactions of the two groups were observed and compared.The levels of VEGF and quality of life were compared before and after the treatment.The stress response indexes such as cortisol (Cor),norepinephrine (NE) and total antioxidant capacity (TAC) were detected,and the stress levels of the two groups were compared.Results The total effective rate of the study group was 67.5％ (54/80),which was significantly better than that of the control group [45.0％ (36/80)],and the difference was statistically significant (x2 =8.229,P =0.004).The quality of life of the two groups after the treatment was significantly higher than that before the treatment,and the quality of life scores of the study group were significantly higher than those of the control group (all P ＜ 0.001).After the treatment,the levels of Cor,NE and TAC of the study group were (239.27 ± 19.63) μg/L,(258.46 ± 18.31) ng/L,(11.01 ± 0.77) KIU/L,which were significantly lower than those of the control group [(286.35 ± 20.63) μg/L,(294.18± 21.95) ng/L,(12.73 ± 1.58) KIU/L],and the differences were statistically significant (t =10.003,P ＜ 0.001;t =9.476,P ＜ 0.001;t =6.984,P ＜ 0.001).After the treatment,the VEGF levels of the two groups were lower than those before the treatment,and the VEGF level of the study group was significantly lower than that of the control group [(39.4 ±0.9) pg/ml vs.(42.3 ± 1.1) pg/ml,t =18.251,P ＜ 0.001].The total incidences of adverse reactions in the control group and the study group were 82.5％ (66/80) and 48.8％ (39/80),respectively.The incidence of adverse reactions in the control group was significantly higher than that in the study group,and the difference was statistically significant (x2 =20.197,P ＜ 0.001).Conclusion Calcium levofolinate and 5-fluorouracil combined with epirubicin has a good clinical effect in treating patients with gastric cancer.It can not only improve the level of VEGF in the serum of patients,but also can improve the quality of life of patients,reduce the incidence of adverse reactions and body stress response.It has broad application prospects and is worthy of further promotion and application in clinic.
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OBJECTIVE： To study the improvement effects and its mechanism of erythropoietin derivative helix B surface peptide （HBSP） on epirubicin-induced myocardial injury in rats. METHODS： SD rats were randomly divided into control group， model group， erythropoietin （EPO） group and HBSP group， with 10 rats in each group. Except for control group， other groups were given epirubicin 2.5 mg/kg intraperitoneally， once a week， for consecutive 6 weeks to induce myocardial injury model. EPO group and HBSP groups were given rhEPO 5 000 u/kg or HBSP 60 μg/kg intraperitoneally， 3 times a week （one day before medication， first day and third day after medication of epirubicin）， for consecutive 6 weeks. At the beginning of the first administration， the rats were weighed at the 11th week. The cardiac function was measured by echocardiography [left ventricular end-diastolic diameter （LVIDd）， ejection fraction （EF）， fractional shortening （FS） and cardiac output（CO）]. The serum levels of troponin I （cTnI） and amino-terminal B-type natriuretic peptide （NT-proBNP） were determined by ELISA. mRNA expression of PI3K and Akt in myocardial tissue was detected by RT-PCR. The protein expression of p-PI3K and p-Akt in rat myocardium were detected by Western blot. RESULTS： During research period， two rats died in model group， one in EPO group and none in HBSP group. Compared with control group， body weight， the levels of EF， FS and CO were decreased significantly in model group， while the contents of LVIDd and cTnI， NT-proBNP were increased significantly； mRNA expression of PI3K and Akt as well as protein expression of p-PI3K and p-Akt were decreased significantly， above differences were statistical significant （P＜0.05）. Compared with model group， body weight， the levels of EF， FS and CO were increased significantly in EPO group and HBSP group， while the contents of LVIDd and cTnI， NT-proBNP were decreased significantly； mRNA expression of PI3K and Akt as well as protein expression of p-PI3K and p-Akt were increased significantly， above differences were statistical significant （P＜0.05）. Compared with EPO group， the contents of cTnI and NT-proBNP were decreased significantly in HBSP group， with statistical significance （P＜0.05）. CONCLUSIONS： HBSP can improve myocardial injury in rats as much as EPO， and has less toxity. Their mechanism may be related to the activation of PI3K/Akt signaling pathway.
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PURPOSE: Epirubicin is one of the most effective drugs against osteosarcoma. miR-1301 is involved in the occurrence and development of osteosarcoma. Whether miR-1301 is responsible for the chemosensitivity of osteosarcoma cells to epirubicin remains largely unknown. MATERIALS AND METHODS: U2OS and SAOS-2 cells were treated with various concentrations of epirubicin. Flow cytometry was employed to evaluate cell apoptotic rate. Cell proliferation was measured by Cell Counting Kit-8 assay. Western blot and quantitative real-time polymerase chain reaction were utilized to detect the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 assaciated X protein (Bax), cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerases (PARP1), TP53-regulated inhibitor of apoptosis 1 (TRIAP1), and microRNA-1301 (miR-1301). The relationship between miR-1301 and TRIAP1 was determined by luciferase reporter assay. RESULTS: Epirubicin inhibited proliferation in a dose-dependent manner, induced apoptosis, decreased the expression of Bcl-2, and increased the expressions of Bax, cleaved-caspase-3, and cleaved-PARP1 in osteosarcoma cells. miR-1301 was downregulated in U2OS and SAOS-2 cells. Importantly, epirubicin significantly increased the levels of miR-1301. Overexpression of miR-1301 suppressed proliferation and promoted apoptosis. Interestingly, those effects were enhanced by epirubicin. In contrast, miR-1301 depletion attenuated the epirubicin-mediated anti-osteosarcoma effect. miR-1301 negatively regulated the expression of TRIAP1 in U2OS and SAOS-2 cells. Furthermore, epirubicin inhibited the mRNA and protein levels of TRIAP1 by upregulating miR-1301 levels. Epirubicin suppressed cell proliferation by downregulating TRIAP1. CONCLUSION: miR-1301 was implicated in the chemosensitivity of osteosarcoma to epirubicin by modulating TRIAP1.
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Apoptosis , B-Lymphocytes , Blotting, Western , Cell Count , Cell Proliferation , Epirubicin , Flow Cytometry , Luciferases , Osteosarcoma , Real-Time Polymerase Chain Reaction , RNA, MessengerABSTRACT
Objective • To compare the therapeutic effects and adverse effects between regimes TEC (docetaxel, epirubicin and cyclophosphamide)×8 and TEC×6 on the adjuvant chemotherapy of locally advanced breast cancer patients. Methods • Sixty-six locally advanced breast cancer patients with at least 4 positive lymph nodes were retrospectively selected in the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine from April 2008 to April 2015. Patients were divided into TEC×8 regime group (n=31) and TEC×6 regime group (n=35) according to the cycles that were given to the patients. Three-year overall survival (OS) and 3-year disease free survival (DFS) rate of patients in these two groups were compared. The incidence of myelosuppression, fever and liver function injury were also compared between patients in TEC×8 regime group and TEC×6 regime group. Chi square test (χ2) was used for comparison between two groups. Kaplan-Meier method was adopted to perform survival analysis. Results • No significant difference was found in 3-year OS rate between TEC×8 regime group (93.5%) and TEC×6 regime group (91.4%) (P=0.716), and no significant difference was found in 3-year DFS rate between TEC×8 regime group (87.1%) and TEC×6 regime group (85.7%) (P=0.855). The incidence of grade III/ myelosuppression of patients in TEC×8 regime group (90.3%) was significantly higher than that in TEC×6 regime group (65.7%) (P=0.017). No significant difference was found in the incidence of fever between TEC×8 '72egime group (16.1%) and TEC×6 regime group (14.3%) (P=0.835). There was no significant difference in the incidence of liver function injury between TEC×8 regime group (77.4%) and TEC×6 regime group (85.7%) (P=0.383). Conclusion • There is no significant difference in OS or DFS rate between TEC×8 regime and TEC×6 regime in adjuvant chemotherapy of locally advanced breast cancer, neither is in the incidence of fever and liver function injury. However, grade III / myelosuppression more frequently occurs in TEC×8 regime group.
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Objective To investigate the effect of L-carnitine (LCNT) combined with epirubicin (EPI) on cell proliferation and apoptosis of two lung adenocarcinoma cell lines (GLC-82 and A549). Methods GLC-82 and A549 cells were divided into control group, EPI group, LCNT group and EPI+LCNT group, respectively. The cell proliferation rate was examined by MTT assay 24 h after the treatment, and the cell cycle and cell early apoptosis were analyzed by flow cytometry. The expression of P53 and Bcl-2 proteins were detected by Western Blot. Results Compared with the control group, the proliferation rate of GLC-82 and A549 cells was 37.56％(P<0.01) and 6.32％(P>0.05) after 24 hours of 20.00μg/ml LCNT treatment indicating LCNT could promote the proliferation of GLC-82 cells. Compared with the EPI group, EPI+LCNT had smaller inhibitory effect on the proliferation of GLC-82 cells, and the inhibition rate of the EPI+LCNT group was 12.14％lower than that of EPI group (P<0.05). Compared with the EPI group, EPI+LCNT could significantly increase the G0/G1 phase ratio of GLC-82 cells (50.42％±1.21％vs. 25.94％± 0.66％, P<0.01) and A549 cells (54.92％±1.71％vs. 38.63％±0.69％, P<0.01), decrease the S phase ratio of GLC-82 cells (34.21％±0.96％vs. 59.68％±1.25％, P<0.05), and prevent the early apoptosis of GLC-82 cells without affecting apoptosis of A549 cells. Moreover, in the EPI+LCNT group, the expression of P53 protein in GLC-82 and A549 cells was down-regulated (P<0.05), and the expression of Bcl-2 protein in GLC-82 cells was up-regulated (P<0.01) and no significant change in A549 cells (P>0.05). Conclusions Comparing with the EPI, the combination of LCNT and EPI has less proliferation inhibition and apoptosis induction on GLC-82 cells, and without significant effect on A549 cells. LCNT can promote the proliferation of GLC-82 cells and block the cell cycle at G0/G1 phase. This mechanism may be related to down-regulation of P53 protein and up-regulation of Bcl-2 protein expression.
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Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.
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Present work is aimed to develop a simple, sensitive, robust and reliable HPLC method for routine quality control of epirubicin (EPI) in bulk drug, marketed injections and polymeric nanoparticles. Separation was carried out by C18 column. Isocratic elution was carried out using mobile phase A: 0.16% o-phosphoric acid solution, B: acetonitrile and methanol mixture (80:20, v/v) in the ratio of 60:40 (A: B) while the flow rate was maintained at 1mL/min. Analyses were performed at 233.5 nm using PDA detector. Excellent linear relationship was observed between peak-area versus drug concentration in the range of 1.0-100.0 µg/mL (r2, 0.999). Developed method was found to be sensitive (Limits of detection and quantification were found to be ~8 ng/mL and ~25 ng/mL, respectively), precise (RSD <1.0%, for repeatability and <2.0% for intermediate precision, within acceptable ranges of precision), accurate (recovery in different dosage form, 94.65 -100.26%, within acceptable range, 80-120%), specific and robust (% RSD <2, for system suitability parameters). Stress-induced degradation studies demonstrated that method can suitability be applied in the presence of degradants. Developed method has been successfully applied for the determination of entrapment efficiency, drug loading, in vitro release profile, in vitro permeation studies as well as stability assessment of polymeric nanoparticles
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Quality Control , Epirubicin/pharmacology , Chromatography, High Pressure Liquid/methods , In Vitro Techniques/instrumentation , Nanoparticles/analysisABSTRACT
Objective To observe the clinical efficacy and side effects of docetaxel combined with epirubicin dose-dense regimen and convention regimen neoadjuvant chemotherapy in patients with triple negative breast cancer.Methods Eighty-one patients with triple negative breast cancer from January 1, 2008 to December 31, 2011 were selected, and they were divided into dose-dense group (40 cases)and convention group(41 cases).All the patients received 2-6 cycles of docetaxel combined with epirubicin neoadjuvant chemotherapy.Chemotherapy scheme was intravenous drip of docetaxel (75 mg/m2)for 1 h and intravenous drip of epirubicin(90 mg/m2)in Day 1.Every 14 d was 1 cycle in dose-dense group,every 21 d was 1 cycle in convention group.The clinical efficacy and side effects of 2 groups were observed and compared, and the 5-year survival rates were analyzed.Results All patients were evaluated.The pathologic complete response rate and the response rate in dose-dense group were significantly higher than those in convention group:20.0%(8/40)vs.12.2%(5/41)and 85.0%(34/40)vs.70.7%(29/41),and there were statistical differences(P<0.05).The 5 years disease-free survival rate and overall survival rate in dose-dense group were higher than those in convention group: 77.5%(31/40)vs.58.5%(24/41)and 87.5%(35/40)vs.73.2%(30/41),and there were statistical differences(P<0.05).In side effects, there were no statistical differences in the incidences of bone marrow suppression, gastrointestinal reactions, abnormal liver function and hair loss between 2 groups (P > 0.05).Conclusions In the neoadjuvant chemotherapy of triple negative breast cancer, compared with convention regimen, the dose-dense regimen can receive higher pathologic complete response rate and response rate,prolong disease-free survival rate and overall survival rate.Side effects is similar,and it is worth to be used in clinic.
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Objective:To prepare biotin-poloxamer(BP) conjugate micelles for epirubicin through biotin conjugated on poloxam-er. Methods:Epirubicin(EPI) was encapsulated in BP micelles. The EPI-loaded BP micelles were characterized by its particle size, zeta potential,surface morphology,as well as the efficiency of drug loading and drug encapsulation and drug release. Marrow leukemia HL-60 cells were used to evaluate the cell cytotoxicity of EPI-loaded BP micelles in vitro. The tumor model in nude mice was estab-lished through the subcutaneous injection of HL-60 cells, and then the inhibitory effect of EPI-loaded BP micelles on tumor volume growth was investigated.Results:It was found that the average particle size of EPI-loaded BP micelles was about 100 nm. In addition, the enhanced cellular uptake ability of EPI-loaded BP micelles was proved by fluorescence microscope observation. The efficiency order of the tumor volume growth inhibition was:EPI-loaded BP micelles > EPI-loaded MATP micelles> EPI-loaded poloxamer micelles>EPI. BP micelles showed significant antitumor activity and low toxicity when compared with the non-targeted micelles. Conclusion:With the advantages of EPR effect and tumor-targeting potential,BP conjugate micelles might be developed as a new system for chemo-therapeutics. However,the tumor targeting technique should be demonstrated further by the other cell experiments and large animal ex-periments.
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Objective To investigate whether TG2 promotes drug resistance to epirubicin through AKT signal pathway in breast cancer. Methods MCF-7 cells with constant expression of TGM2 gene(TGM2-LV)were established via the lentiviral vector. The breast cancer cells were divided into five groups,including the NC group, TG2 group and MK2206 group. The MCF-7/adr cells were divided into ADR group and MKadr group. The expres-sion of TG2 ,AKT ,Bcl-2 and P53 was detected by Western blot assay. Cells were treated with epirubicin. MTT assay was performed to assess cell proliferation. The inhibition ratio of cancer cell proliferation was evaluated. TUNEL analysis was performed to identify the apoptosis of the breast cancer cells. Results Lvels of TG2,p-AKT and Bcl-2 in NC group were significantly lower than those in TG2 group,while the expression of P53 in NC group was much higher. In MK2206(or MK/adr )group,p-AKT and Bcl-2 were down-regulated,while P53 was markedly up-regulated compared with TG2(or ADR)group(P<0.05). The results of the MTT assay showed a strong inhibi-tion in cell proliferation rate in MK2206(or MKadr )group. Compared with the NC group,TG2 promoted prolifera-tion of MCF-7 cells in TG2 group. The cell apoptosis rate in MK2206(or MKadr )group was significantly higher than that in TG2(or ADR)group(P<0.05). TG2 significantly inhibit the apoptosis of breast cancer cells ,com-pared to the control group. Conclusion TG2 might promote drug resistance to epirubicin through AKT signal path-way in breast cancer
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Objective To compare the clinical efficacy and safety of docetaxel combined with carboplatin (TP) and epirubicin combined with cyclophosphamide sequential docetaxel (EC-T) adjuvant in the treatment of three negative breast cancer in phase III . Methods 62 cases of three negative breast cancer patients in phase III from May 2012 to October 2016 were selected and randomly divided into the control group and the experimental group, with 31 patients in each group. The control group was treated with epirubicin combined with cyclophosphamide and sequential docetaxel, and the experimental group was treated with docetaxel and carboplatin. The clinical indicators were compared and analyzed. Results There was no significant difference in the recent remission rate (77.42%) between the experimental group and the control group (74.19%). Two groups of patients with adverse reactions were restored within one month. There were 10 cases of WBC decrease in the experimental group, with the incidence rate of 32.25%. There were 18 cases of WBC decrease in the control group, the incidence rate was 58.06%, the difference was statistically significant (P<0.05). Conclusion Docetaxel combined with carboplatin and epirubicin adjuvant combined with cyclophosphamide than star sequential docetaxel in the treatment of three patients with negative breast cancer stage III were tolerated, TP occurred leukopenia and alopecia with low probability.
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Objective To investigate whether TG2 promotes drug resistance to epirubicin through AKT signal pathway in breast cancer. Methods MCF-7 cells with constant expression of TGM2 gene(TGM2-LV)were established via the lentiviral vector. The breast cancer cells were divided into five groups,including the NC group, TG2 group and MK2206 group. The MCF-7/adr cells were divided into ADR group and MKadr group. The expres-sion of TG2 ,AKT ,Bcl-2 and P53 was detected by Western blot assay. Cells were treated with epirubicin. MTT assay was performed to assess cell proliferation. The inhibition ratio of cancer cell proliferation was evaluated. TUNEL analysis was performed to identify the apoptosis of the breast cancer cells. Results Lvels of TG2,p-AKT and Bcl-2 in NC group were significantly lower than those in TG2 group,while the expression of P53 in NC group was much higher. In MK2206(or MK/adr )group,p-AKT and Bcl-2 were down-regulated,while P53 was markedly up-regulated compared with TG2(or ADR)group(P<0.05). The results of the MTT assay showed a strong inhibi-tion in cell proliferation rate in MK2206(or MKadr )group. Compared with the NC group,TG2 promoted prolifera-tion of MCF-7 cells in TG2 group. The cell apoptosis rate in MK2206(or MKadr )group was significantly higher than that in TG2(or ADR)group(P<0.05). TG2 significantly inhibit the apoptosis of breast cancer cells ,com-pared to the control group. Conclusion TG2 might promote drug resistance to epirubicin through AKT signal path-way in breast cancer
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AIM:To observe the effects of the combination of berberin and epirubicin on the cell cycle of T24 bladder cancer cells and the underlying mechanisms.METHODS:The cancer cells were exposed to epirubicin in the presence or absence of different concentrations of berberin.The viability of the cancer cells was determined by MTT assay.The cell cycle distribution was detected by flow cytometry, and the protein levels of cyclin D1, CDK2, CDK4, P21 and P27 were detected by Western blot.RESULTS:Berberine markedly enhanced the inhibitory effect of epirubicin on the viability of T24 cells and promoted epirubicin-induced cell cycle arrest at G0/G1 phase as compared with the negative control cells.Epirubicin increased the protein expression of P27 and P21, both of which were enhanced by treatment with berberin.In contrast, berberin exposure further decreased the protein expression of cyclin D1, CDK2 and CDK4 in epirubicin-treated T24 cells.CONCLUSION:Berberine significantly promotes epirubicin-induced G0 /G1 phase arrest in human bladder cancer cells by up-regulating P27 and P21 expression and inhibiting the expression of cyclin D1, CDK2 and CDK4.
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OBJECTIVE:To investigate the effects of neoadjunctive chemotherapy(NAC)of docetaxel and epirubicin com-bined with cyclophosphamide on clinical efficacy and tumor markers of breast cancer patients with different molecular types. METH-ODS:A total of 88 female patients with locally advanced breast cancer collected from our hospital during Jan. 2014-Jan. 2016 were divided into Luminal A type(23 cases),Luminal B type(21 cases),basal-like type(11 cases),HER2-over expressing type(18 cases)and normal breast-like type(15 cases)according to molecular type. All patients were given Docetaxel injection+Epirubicin hydrochloride injection+Cyclophosphamide for injection for consecutive 6 cycles(21 d as a cycle). Total response rates and patho-logical complete remission(pCR)rates were compared among breast cancer patients with different molecular types. The expression of serum tumor markers [CEA,CA125,CA153] were compared before and after treatment,and the occurrence of ADR was record-ed. RESULTS:Total response rate of 88 patients was 63.64%,among which that of basal-like breast cancer patients was 72.73%, significantly higher than other molecular types,with statistical significance(P0.05). The pCR rate of 88 patients was 27.27%,and that of basal-like breast cancer patients was the highest(45.45%). There was statistical significance in pCR rates of pairwise molecular type compari-son(P0.05). Before treatment,there was no statistical significance in the expression of CEA,CA125 and CA153 in breast can-cer patients with different molecular types(P>0.05). After treatment,the expression of CEA,CA125 and CA153 in different mo-lecular types were decreased significantly,with statistical significance(P0.05). There was no statistical significance in the incidence of ADR among different molecular types(P>0.05). CONCLUSIONS:NAC plan of docetaxel and epirubicin combined with cyclophospha-mide can reduce the expression of tumor markers and shows certain therapeutic efficacy for breast cancer patients with different mo-lecular types. Total response rate and pCR rate of basal-like type are better than those of other molecular types,so NAC plan is the preferred treatment for basal-like type breast cancer.