• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.3
• /
• pp.1721-1724
• /
• 2013

Objective: To investigate the effect of epirubicin on soluble CD25 (sCD25) secretion by CD4+CD25+ regulatory T (Treg) cells isolated from diffuse large B-cell lymphoma (DLBCL) patients. Methods: Treg cells were isolated from the peripheral blood mononuclear cells isolated from the newly diagnosed DBLCL patients. The concentration of sCD25 in the supernatant was determined with a commercial sCD25 (IL-2R) enzyme-linked immunosorbent assay (ELISA) kit. The fluorescence intensity of CD25 was detected by flow cytometry. Results: Cell survival rate was significantly decreased along with the increase of epirubicin concentration after treatment for 24 h. There was also a significant difference in the concentration of sCD25 between the epirubicin group and the control group (P<0.01). A positive correlation between the Treg cells survival rate and the concentration of sCD25 was detected (r=0.993, P<0.01). When equal numbers of CD4+CD25+ Treg cells of the epirubicin group and the control group were cultured for another 24 h without epirubicin the CD25 fluorescence intensity on the surface of Treg cells was obviously higher in the epirubicin group than that in the control group (P<0.01), while the sCD25 concentration in the supernatant in the epirubicin group was significantly lower than that in the control group (P<0.05). Conclusion: Epirubicin may improve the body's immune functions by inhibiting the sCD25 secretion by Treg cells in DLBCL patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.12
• /
• pp.7171-7177
• /
• 2013

Purpose: To compare the safety and efficacy of first-line chemotherapy regimen with or without doxorubicin in treating patients with advanced soft tissue sarcoma (STS). Patients and Methods: We retrospectively analyzed a cohort of 56 patients histologically confirmed with STS who were treated at Jiangsu Cancer Hospital and Research Institute from July 2011 to June 2012.The basic element of first line chemotherapy contained epirubicin in group B and lacked epirubicin in group A. Response was assessed using RECIST criteria. The Kaplan-Meier method was used to estimate progress free survival (PFS). Results: According to RECIST criteria, patients in group treated by chemotherapy without epirubicin, the objective response (OR) ratio was 6.5 % (CR0%+PR6.5%). Disease control rate (DCR=CR+PR+SD) was 25.8% with a median follow-up of 14.6 months, including 2 patients achieving a partial response (PR 6.5%) and a stable response (SD 19.4%) in 6. In group B with epirubicin based regimens, no patient had complete response, PR (28 %) was observed in 7 and SD (24 %) in 6. DCR was observed in 13 patients (52%). By Fisher's exact test, the DCR difference between the two groups was statistically significant (p=0.046). In group A, median PFS was 3.0 months (95%CI:2.1-3.8), compared with 4.0 months (95% CI:3.03-4.97) in group B (p=0.0397 by log-rank test). Epirubicin based chemotherapy and ECOG performance status 0-1 were identified as favorable factors for progression in our cohort of patients. Differences of nonhematologic and hematologic toxicities were not statistically significant between the two groups, and the addition of epirobicin was not associated with cardiac toxicity (p=0.446). Conclusion: Our study demonstrates that epirubicin-based chemotherapy is effective and well tolerated, and is superior to chemotherapy without epirubicin regarding efficacy. Therefore it is recommended that epirubicin-based chemotherapy should be considered as first line for patients with advanced STS.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.10
• /
• pp.5849-5854
• /
• 2013

Background: Apoptosis may be induced after Bcl-2 expression is inhibited in proliferative cancer cells. This study focused on the effect of autophagy activation by ABT737 on anti-tumor effects of epirubicin. Methods: Cytotoxic effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay and cell apoptosis through flow cytometry. Mitochondrial membrane potential was measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1, apoptotic or autophagy related proteins, was detected by Western blotting. Results: ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose- and time-dependent manner. Both ABT737 and epirubicin alone could induce cell apoptosis with a reduction in mitochondrial membrane potential as well as increased apoptotic protein expression. Further increase of apoptosis was detected when HepG2 cells were co-treated with ABT373 and epirubicin. Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate cell autophagy with elevated autophagosome formation, increased expression of autophagy related proteins and LC3 fluorescent puncta. Conclusions: ABT737 influences cancer cells through both apoptotic and autophagic mechanisms, and ABT737 may enhance the effects of epirubicin on HepG2 cells by activating autophagy and inducing apoptosis.

• Journal of Ginseng Research
• /
• v.39 no.1
• /
• pp.22-28
• /
• 2015

Background: Sun ginseng (SG), a specific formulation of quality-controlled red ginseng, contains approximately equal amounts of three major ginsenosides (RK1, Rg3, and Rg5), which reportedly has antitumor-promoting activities in animal models. Methods: MTT assay was used to assess whether SG can potentiate the anticancer activity of epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells; apoptosis status was analyzed by annexin V-FITC and PI and analyzed by flow cytometry; and apoptosis pathway was studied by analysis of caspase-3, -8, and -9 activation, mitochondrial accumulation of Bax and Bak, and cytochrome c release. Results: SG remarkably enhances cancer cell death induced by epirubicin or paclitaxel in human cervical adenocarcinoma HeLa cells, human colon cancer SW111C cells, and SW480 cells. Results of the mechanism study highlighted the cooperation between SG and epirubicin or paclitaxel in activating caspase-3 and -9 but not caspase-8. Moreover, SG significantly increased the mitochondrial accumulation of both Bax and Bak triggered by epirubicin or paclitaxel as well as the subsequent release of cytochrome c in the targeted cells. Conclusion: SG significantly potentiated the anticancer activities of epirubicin and paclitaxel in a synergistic manner. These effects were associated with the increased mitochondrial accumulation of both Bax and Bak that led to an enhanced cytochrome c release, caspase-9/-3 activation, and apoptosis. Treating cancer cells by combining epirubicin and paclitaxel with SG may prove to be a novel strategy for enhancing the efficacy of the two drug types.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.16
• /
• pp.6849-6853
• /
• 2014

Multidrug resistance (MDR) is a major impediment to successful chemotherapy of gastric cancer. Our aim was to establish an epirubicin-resistant cell subline (AGS/EPI) and to elucidate the mechanisms involved in acquired EPI resistance. The AGS/EPI cell subline developed by exposing parental AGS cells to stepwise increasing concentrations of EPI demonstrated 2.52-fold resistance relative to the AGS cell line, and mRNA expression of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), more recently known as ABCB1 protein, was similarly upregulated. An AGS/EPI cell subline could thus be effectively established, and MDR mechanism of these cells was shown to be related to the overexpression of mRNA of the ABCB1 gene.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.250.2-251
• /
• 2003

There are contradicting reports on the nephrotoxicity of heptaplatin, a new platinum derivative. A retrospective study was performed to compare the toxicities of heptaplatin-containing regimens with the ones not. Seventy-seven patients with advanced gastric cancer who did not receive any chemotherapy within the last 3 months before the treatment were evaluated. Among them 38 patients received heptaplatin-containing regimens (heptaplatin/epirubicin/5-FU: 26, heptaplatin/5-FU: 12) and 39 patients received other regimens (cisplatin/epirubicin/5-FU:11, epirubicin/leucovorin/5-FU: 28). (omitted)

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.428.1-428.1
• /
• 2002

Gemcitabine demonstrated modest activity in locally advanced and metastatic pancreatic cancer with difficulty early diagnosis and poor prognisis. The purpose of this study was to evaluate the efficacy and toxicity of gemcitabine and 5-fluorouracil(GF) combination theraphy and epirubicin. cisplatin. and 5-fluorouracil(ECF) combination theraphy for the patients with locally advanced or metaststic pancreatic cancer. Between January 1996 and December 2001. (omitted)

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.1
• /
• pp.131-133
• /
• 2016

Background: Combination chemotherapy regimes are common treatments for cancer. The aim of this study was to evaluation the effect of individual chemotherapeutic agents in comparison with a first line chemotherapy regime treatment in the AGS gastric cancer cell line by MTT assay. Materials and Methods: In this experimental study, AGS cells were grown in RPMI-1640 supplemented with 10% fetal calf serum and 100 IU/ml penicillin, and $10{\mu}g/ml$ streptomycinin, under a humidified condition at $37^{\circ}C$ with 5% CO2. All cells were washed with PBS and detached with trypsin, centrifuged and 8000 cells re-plated on to 96- well plates. LD50 doses of Epirubicin, Cisplatin and 5-fluorouracil were added to each well in mono or triple therapy. Anti-proliferative activities were determined by MTT assay after 24, 48 or 72 h. Results: Results of MTT assays showed that there were no significant differences among 3 drugs in monotherapy (p=0.088), but there was significant difference between combination therapy with epirubicin (P=0.031) and 5FU (p=0.013) on cell survival at 24 h. After 48 and 72 hours, cell viability showed significant differences between the 3 drugs (p=0.048 and P=0.000 for 48 and 72 h, respectively) and there was significant difference between combination therapy with epirubicin (P=0.035 and P=0.002 for 48 and 72 h, respectively). Conclusions: The results showed no significant differences between these chemotherapy drugs each given alone, but combination therapy with 3 drugs had significant effects on cell viability in comparison with epirubicin alone.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.8
• /
• pp.3651-3657
• /
• 2014

Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC.

• Korean Journal of Clinical Pharmacy
• /
• v.16 no.2
• /
• pp.131-138
• /
• 2006

Heptaplatin, a new platinum derivative, has several contradicting reports on the nephrotoxicity. Therefore, the aim of this study is to compare the toxicities of heptaplatin-containing regimens in the chemotherapy. This study was performed retrospectively on seventy-seven patients with advanced gastric cancer who did not receive chemotherapy within the last 1 months before taking of heptaplatin- or cisplatin-containing chemotherapy. The 38 patients among total patients was received heptaplatin-containing regimens (26 with SEF regimens: heptaplatin/epirubicin/5-FU, 12 with SF regimens: heptaplatin/5-FU) and the rest 39 patients was received cisplatin-containg regimens (11 with CEF regimens: cisplatin/epirubicin/5-FU, 28 with ELF regimens: epirubicin/leucovorin/5-FU). Before and after the chemotherapy serum creatinine (Scr) and proteinuria were measured by urine stick test in all patient groups. Also Scr was measured a day before the second cycle and did not vary significantly between groups. However Scr on cycle 3 were significantly higher in SEF and SF groups. In case of proteinuria, it was more frequent on cycle 1 in heptaplatin/5-FU group. Proteinuria before and after on cycle 2 was not different between the two cisplatin -containing groups, but was more frequent in heptaplatin-containing groups. The reason why the Scr measured was not so different could be because we excluded the patients who received only one cycle of heptaplatin and changed the regimen due to signs of nephrotoxcity. As the results nephrotoxicity such as protienuria was appeared to be more frequent with heptaplatin-treated patients. It suggests that the clinical consequences of the toxicity need to further evaluation and also the modalities to prevent or minimize nephrotoxicity of heptaplatin should be studied for future utilization of the drug.