OBJECTIVE: To investigate the therapeutic effect of spleen low molecular weight extracts on epileptics hydrochloride-induced leukopenia in mice and explore its mechanism. METHODS: The model of leukopenia in mice was established by the injection of epirubicin hydrochloride (10 mg/kg). After the injection of chemotherapeutic drugs, leukocytopenia mice were treated with different doses of spleen low molecular weight extract, Ganoderma oral solution and recombinant granulocyte colony stimulating factor (rhG-CSF). The general survival status indicators such as body weight, coat color and athletic ability of mice in each group were recorded; the tail vein blood of mice in each group was collected and the white blood cell count in them was calculated; bone marrow of mice was taken and bone marrow smears were observed. RESULTS: In the model group, the weight of the mice gradually decreased in the later period, their coat became dark and rough, and the ability to exercise decreased, while the mice in the treatment groups showed different degrees of improvement in their survival status except for the mice treated by rhG-CSF. There was no significant fluctuation in the white blood cell count of the blank control mice. After injection of epirubicin, the white blood cell count of peripheral blood in the model mice and treated mice were decreased. The white blood cell count was lower in the mice treated with high-dose low molecular weight extract and rhG-CSF than that in other experimental groups. Bone marrow smear showed that the proportion of bone marrow nucleated cells in the mice treated with the low molecular weight extract of the spleen was significantly higher than that of model mice (P<0.05). CONCLUSION The low molecular weight spleen extracts can significantly improve the hematopoietic state of mouse bone marrow, promote the proliferation of inhibited bone marrow cells, and thus has the effect of treating leukopenia in mice.
Animals ; Epirubicin ; Granulocyte Colony-Stimulating Factor ; Leukocyte Count ; Leukopenia/drug therapy* ; Mice ; Molecular Weight ; Plant Extracts ; Recombinant Proteins ; Spleen

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.
Apoptosis ; B-Lymphocytes ; Blotting, Western ; Cell Count ; Cell Proliferation ; Epirubicin ; Flow Cytometry ; Luciferases ; Osteosarcoma ; Real-Time Polymerase Chain Reaction ; RNA, Messenger

To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC).The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy. The response to treatment, disease recurrence, complications and adverse effects were documented and compared between two groups.There were no significant differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and disease control rate (CR+PR+SD), disease recurrence, complications and adverse effects of interventional therapy between cTACE group and DEB-TACE group. Additionally, there were no significant differences about locoregional biliary injuries, intrahepatic biloma, and newly detected intra- or extrahepatic HCC on MRI between cTACE group and DEB-TACE group.There were no statistically significant differences between cTACE group and DEB-TACE group with regard to the short-term response, disease recurrence, complications and side effects. Hepatic-locoregional complications may be more frequent in DEB-TACE group than those in cTACE group.
Carcinoma, Hepatocellular ; diagnostic imaging ; therapy ; Chemoembolization, Therapeutic ; adverse effects ; instrumentation ; methods ; Comparative Effectiveness Research ; Drug Delivery Systems ; instrumentation ; methods ; Epirubicin ; administration & dosage ; therapeutic use ; Humans ; Liver Neoplasms ; Magnetic Resonance Imaging ; Microspheres ; Neoplasm Recurrence, Local ; Retrospective Studies ; Treatment Outcome

PURPOSE: Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. MATERIALS AND METHODS: We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. RESULTS: Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. CONCLUSIONS: EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resection, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.
Capecitabine* ; Chemotherapy, Adjuvant ; Cohort Studies ; Disease-Free Survival ; Drug Therapy* ; Epirubicin* ; Follow-Up Studies ; Gastrectomy ; Gastric Outlet Obstruction ; Humans ; Lymph Node Excision ; Lymph Nodes ; Multivariate Analysis ; Postoperative Complications ; Retrospective Studies ; Stomach Neoplasms* ; Survival Analysis* ; Survival Rate

To study the impact of single instillation of epirubicin (SIE) on the cancer recurrence of non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT) in Korean patients. The major inclusion criteria were NMIBC patients. The major exclusion criteria were muscle invasive bladder cancer, metastatic bladder cancer, combined urinary upper tract tumor, and carcinoma in situ. SIE group received 50 mg epirubicin within 6 hours after TURBT. Non-SIE group did not receive epirubicin. This study enrolled a total of 214 patients diagnosed as having NMIBC during the period from October 2003 through January 2010 at the single institutions. Follow-up of the patients was conducted through January 2012. The median age of patients was 63.4 years. Of 112 evaluable patients in the SIE group, cancer recurrence rate was 33.9% and in non-SIE group, cancer recurrence rate was 62.7% (p<0.001). The recurrence-free survival duration was longer in Group SIE compared with Group non-SIE (p<0.001). Multivariate analysis revealed that SIE was significantly associated with cancer recurrence (HR 0.213, p<0.001). We confirmed the impact of SIE on the cancer recurrence in the Korean patients who underwent TURBT for NMIBC. Single instillation of chemo-agent after TUR-B might be recommended in Korean patients for reduce bladder cancer recurrence and provide longer recurrence-free survival duration.
Carcinoma in Situ ; Epirubicin* ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Recurrence ; Urinary Bladder Neoplasms* ; Urinary Bladder*

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

BACKGROUND/AIMS: Metronomic (MET) chemotherapy is a treatment characterized by frequent infusion of low doses of chemotherapeutic agent without extended break. The aim of this study is to evaluate the efficacy of MET chemotherapy compared with transarterial chemoembolization (TACE) in patients with child B class advanced hepatocellular carcinoma (HCC). METHODS: Seventy-three patients with child B class advanced HCC were analyzed between April, 2007 and August, 2013 according to two treatment groups: (i) MET chemotherapy group (n=43, Epirubicin 35 mg/body surface area [BSA] every 4 weeks, and cisplatin 15 mg/BSA and 5-fluorouracil 50 mg/BSA weekly for 3 weeks) via an implantable port system with 1 week break. (ii) TACE group (n=30, Adriamycin 20-50 mg) every 4 weeks. Primary endpoint was overall survival (OS). RESULTS: The median survival times in the MET and TACE groups were 4.5 months and 3.1 months, respectively. The overall survival rate showed significantly better in the MET treatment group than in the TACE group (P=0.039). When the factors affecting patient OS were analyzed, MET chemotherapy (P=0.038, hazard ratio {HR} 0.538 [95% confidence interval {CI} 0.299-0.967]) was independently associated with OS. Larger maximal tumor size, extrahepatic metastasis and advanced stage also were significant factors for OS (P=0.009, HR 1.064 [95% CI 1.014-16.064]; P=0.014, HR 2.120 [95% CI 1.164-3.861]; P=0.019, HR 2.046 [95% CI 1.125-3.720], respectively). CONCLUSIONS: MET chemotherapy showed survival benefit than TACE in patients with child class B advanced HCC. Therefore, MET chemotherapy may be considered as a treatment option for advanced HCC with poor liver function.
Carcinoma, Hepatocellular* ; Child ; Cisplatin ; Doxorubicin ; Drug Therapy* ; Epirubicin ; Fluorouracil ; Humans ; Liver ; Neoplasm Metastasis ; Survival Rate

PURPOSE: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. MATERIALS AND METHODS: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. RESULTS: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. CONCLUSIONS: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.
Adenosine ; Adenosine Triphosphate ; Antibodies ; Cell Death ; Cisplatin ; Doxorubicin ; Drug Screening Assays, Antitumor ; Drug Therapy ; Epirubicin ; Etoposide ; Fluorouracil ; Gastrectomy ; Granzymes ; Humans ; Lymphocytes, Tumor-Infiltrating* ; Methotrexate ; Mitomycin ; Paclitaxel ; Pilot Projects* ; Stomach Neoplasms*

OBJECTIVEThe aim of this study was to analyze the efficacy and safety of paclitaxel liposomal and docetaxel for neoadjuvant chemotherapy of breast cancer.

METHODSWe retrospectively analyzed the clinical data of 188 operable patients with breast cancer who received neoadjuvant chemotherapy. According to the treatment regimens, they were divided into the group of paclitaxel liposome (86 patients) and group of docetaxel (102 patients) treatment. All the patients received a combination therapy with epirubicin and cyclophosphamide, i.e. neoadjuvant chemotherapy with three drugs, 21 days as a cycle, and a total of 6 cycles. Surgery was carried out three weeks after the end of chemotherapy, and the chemotherapy efficacy and adverse reaction of both groups were evaluated.

RESULTSPathological complete response (pCR) rate in the paclitaxel liposome group and docetaxel group was 10.5% and 9.8%, respectively, the objective response rate (ORR) was 80.2% and 79.4%, respectively, and the disease control rate (DCR) was 95.3% and 93.1%, respectively, showing a non-significant difference in therapy efficacy between the two groups (P > 0.05). Safety analysis indicated that all the occurrence rates of skin and nail toxic reaction, body fluid retention, oral mucositis, allergic reaction (such as facial blushing, chest distress, palpitation, dyspnea. etc.), and grade III-IV leukopenia and neutropenia in the paclitaxel liposome group were significantly lower than that of the docetaxel group (all P < 0.05).

CONCLUSIONSCompared with docetaxel, paclitaxel liposome has the same anti-tumor efficacy, but causes fewer and milder adverse reactions with a higher safety in the neoadjuvant chemotherapy for breast cancer.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; Cyclophosphamide ; therapeutic use ; Epirubicin ; therapeutic use ; Female ; Humans ; Liposomes ; Neoadjuvant Therapy ; Neutropenia ; Paclitaxel ; therapeutic use ; Remission Induction ; Taxoids ; therapeutic use

OBJECTIVETo retrospectively investigate the incidence of severe neutropenia and elevation of transaminase during neoadjuvant chemotherapy using epirubicin, cyclophosphamide and fluorouracil in breast cancer patients.

METHODSFrom January 2011 to December 2012, 303 consecutive breast cancer patients with complete treatment data treated in our department were included in this analysis. All patients received neoadjuvant chemotherapy with equal dose of EPI (100 mg/m(2)) administered every 3 weeks for 4 cycles before surgery.

RESULTS200 patients (66.0%) experienced at least one episode of grade 3/4 neutropenia/leukopenia, among them 176 patients experienced their first episode after the first cycle. Febrile neutropenia (FN) occurred in 13 patients for 14 episodes. Elevation of transaminase occurred in a total of 46 patients (15.2%), among them, grade 2 or higher elevation occurred in 15 patients (5.0%). Three blood test plans were adopted to monitor the patients during chemotherapy: (1) Routine blood count repeated every week; (2) Routine blood count before and on day 10 of each chemotherapy episode; (3) Routine blood count before and on day 7, 10 and 14 of each chemotherapy episode. The number of patients whose chemotherapy was delayed due to 3/4 neutropenia/leucopenia in each blood test plan was 3 (5.0%), 7 (3.9%) and 2 (3.2%), respectively. The number of patients with febrile neutropenia (FN) in each blood test plan was 2 (3.3%), 8 (4.4%) and 3 (4.8%), respectively. No statistically significant difference in treatment delay or the incidence of FN was observed among different blood test plans. No statistically significant difference in the incidence of grade 3/4 neutropenia/leukopenia or grade 2 or higher transaminase elevation was observed among different 5-Fu regimens.

CONCLUSIONSDuring neoadjuvant chemotherapy using FE100 C, Fci E100 C or E100 C for breast cancer patients without routine prophylactic G-CSF, the incidence of grade 3/4 neutropenia/leukopenia is 66.0%. With the patient management plan we adopted, 4.3% of patients developed febrile neutropenia. Prophylactic medication may not be necessary for patients without evident liver dysfunction.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; Cyclophosphamide ; therapeutic use ; Epirubicin ; therapeutic use ; Female ; Fluorouracil ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; Humans ; Incidence ; Neoadjuvant Therapy ; Neutropenia ; metabolism ; Retrospective Studies ; Transaminases ; metabolism