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Objective To investigate the effect of silencing MFG-E8 gene on the sensitivity of SKOV3 cells to anticancer drugs and related mechanisms. Methods SKOV3 cells were transfected with MFG-E8 siRNA (Msi) and NC siRNA (Csi), respectively and the efficiency of transfection was confirmed by Western blot. The sensitivity of SKOV3 cells to cisplatin was observed by CCK-8 assay after transfection. The mRNA expression of ABCB1 and ABCC1 were detected by qRT-PCR. Effect of silencing MFG-E8 on the expression of ETM-related protein was detected by qRT-PCR and Western blot. Results MFG-E8 siRNA could effectively silence the expression of MFG-E8 protein. With the increasing drug concentration, the proliferation inhibition rate of each group also increased, and the cell proliferation inhibition rate of MFG-E8 siRNA group increased significantly (P < 0.01). Compared with NC siRNA group, downregulation of MFG-E8 expression led to decreased SKOV3 cell proliferation at 48h or 72h after 3 μg/ml cisplatin treat ment (P < 0.05). qRT-PCR results showed that the mRNA expression of ABCB1 and ABCC1 in Msi group were significantly lower than those in Csi group. qRT-PCR and Western blot results showed that silencing MFG-E8 gene down-regulated the mRNA and protein expression of N-Cadherin, Vimentin and Snail and up-regulated the expression of E-Cadherin. Conclusion Silencing the MFG-E8 gene can increase the sensitivity of SKOV3 cells against anti-tumor drugs and down-regulate the mRNA expression of ABCB1 and ABCC1, which may be related to the inhibition of EMT progression.
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Context: In platinum-resistant ovarian cancer, single-agent chemotherapy is recommended for the reduction of adverse events. However, in clinical practice, some patients can tolerate drug-specific adverse events. Aims: We assessed the safety of pegylated liposomal doxorubicin (PEG-LD) and docetaxel regimen in the first cycle of ovarian cancer. Settings and Design: We performed a phase I study to evaluate the combination therapy of PEG-LD and docetaxel. Materials and Methods: We recruited five patients with recurrent ovarian cancer within 12 months of first-line platinum-based chemotherapy. All patients had measurable disease severity. PEG-LD and docetaxel were intravenously administered on day 1 and every 21 days using three dose levels: 25 mg/m2 PEG-LD and 50 mg/m2 docetaxel; 30 mg/m2 PEG-LD and 50 mg/m2 docetaxel; and 30 mg/m2 PEG-LD and 60 mg/m2 docetaxel. Statistical Analysis Used: We defined the maximum tolerated dose of the combination therapy based on the modified Fibonacci method. Results: Five patients were enrolled in this study. The median treatment-free interval was 5.5 months. Two dose-limiting toxicities (Grade 4 neutropenia) were observed in two patients. One complete response, one partial response, one stable disease, and two progressive disease cases were observed. The overall response rate was 2/5, and the disease control rate was 3/5. The median overall survival was 7.4 months. Conclusions: We determined that 25 mg/m2 of PEG-LD and 50 mg/m2 of docetaxel were safe and effective doses. This preliminary efficacy and safety data should be further investigated in a Phase II trial.
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Objective: To determine the prognostic value of excision repairs cross-complementation group1 (ERCC1) gene in cases with nasopharyngeal carcinoma (NPC) treated with platinum-containing chemotherapy (PCT). Subjects and Methods: The present study was included 33 cases in local advanced stage with NPC. ERCC1 expression was evaluated by using immunohistochemical staining in biopsy specimens. We evaluated the relationship between the degree of ERCC1 expression and clinicopathological features, response to therapy, survival rates in cases with NPC, retrospectively. Results: ERCC1 expression was not observed in 5 (15.15%) of all cases. Thirteen (39.9%) cases weakly positive (+1, +2) and 15 (45.5%) cases of all them were rather strongly positive (+3). There was no statistically significant difference between the degree of ERCC1 expression and clinicopathological features, response to treatment, survival rates (P > 0.05) in cases with NPC. Conclusions: ERCC1 expression has no predictive value for survival in cases locally advanced stage with NPC. Evaluation of ERCC1 expression is not appropriate with a biomarker to detect cases who can benefit from PCT in NPC
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Objective To explore the efficacy and safety of Bevacizumab combined with albumin binding paclitaxel in the treatment of platinum resistant recurrent ovarian cancer.Methods From June 2014 to January 2016,eighty-two recurrent ovarian cancer patients were selected in the study and randomly divided into the treatment group (41 cases) and the control group (41 cases),the control group was treated with albumin binding paclitaxel,and the treatment group was treated with Bevacizumab combined with albumin binding paclitaxel.The clinical efficacy (such as overall response rate,complete response rate,partial response rate,stability of disease,progression of disease),progression free survival (PFS),overall survival (OS) and the adverse reaction rate were compared.Results The total effective rate (ORR) of the experimental group was 85.37％ (35/41),which was significantly higher than that of the control group (65.85％ (27/41),and the difference was statistically significant (P=0.040).The median PFS and OS in the experimental group were 9 (1 ～16) months and 16 (4～26) months,significantly higher than those in the control group (6 (1 ～ 13)months (HR =0.624,95％ CI:0.367 ～ 0.899,P =0.023);12 (2 ～ 25) months (HR =0.603,95％ CI:0.324 ～ 0.791,P =0.009);subgroup analysis showed that the median OS of patienta without metastasis in the experimental and control group were 18 (8 ～ 26) months and 13 (2 ～ 25) months respectively (HR =HR =0.610,95％ CI:0.229 ～ 1.544,P=0.291),and the median PFS was 11 (5～ 16) months and 8 (1 ～ 13) months (HR=0.496,95％CI:0.160～1.046,P=0.089),there were no significant differences;the median P FS in patients with metastasis of the experimental group and the control group were 9 (3～14)months and 6 (1～ 10)months (HR =0.483,95％ CI:0.273 ～ 0.769 months,P＜0.001),the median OS were 14 (4～22) months and 11 (2～20)months (HR =0.556,95％CI:0.197～ 0.569,P=0.008).There was no significant difference in the incidence of adverse reactions between the two groups (12.20％,21.95％,P=0.240).Conclusion Compared with the treatment of albumin binding paclitaxel,in the treatment of platinum resistant recurrent ovarian cancer,the combined treatment of bevacizumab and albumin binding paclitaxel can significantly improve the clinical effect and improve the patients' survival and total survival time.
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OBJECTIVE:To compared with empirical medication and medication under the guidance of adenosine triphos-phate-tumor chemosensitivity assay (ATP-TCA) in the treatment of platinum resistance recurrent ovarian cancer,and to explore clinical efficacy,survival situation of the occurrence of ADR. METHODS:90 cases of platinum resistant recurrent ovarian cancer were divided into drug sensitive group(46 cases)and control group(44 cases)according to admission order. According to clinical experience,control group was given gemcitabine+ifosfamide+doxorubicin for chemotherapy;according to the ATP-TCA test re-sults,chemotherapy plan of drug sensitive group was determined. A treatment course of 2 groups lasted for 28 d,and both received 2-6 courses of chemotherapy. Chemotherapy efficacy,survival situation and the occurrence of ADR were compared between 2 groups. RESULTS:18 cases receiving paclitaxel,14 cases receiving doxorubicin,6 cases paclitaxe+vinorelbine,5 cases gemcitabi-ne,3 cases topotecan in the drug sensitive group. The total effective rate of drug sensitive group was 58.70%,which was signifi-cantly higher than that(36.96%)of control group,with statistical significance(P0.05). CONCLUSIONS:According to ATP-TCA test results,chemotherapy efficacy and survival situation of patients with platinum resistant recurrent ovarian cancer receiving targeted chemotherapy regimen are better than those receiving clinical empirical medication,and the incidence of ADR will not be influ-enced.
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BACKGROUND: Bevacizumab, a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A, was described to be effective in the treatment of recurrent or platinum‑resistance ovarian cancer. The present retrospective study was performed to further evaluate the clinical efficacy and toxicity of bevacizumab in the treatment of Chinese recurrent ovarian cancer patients who had been previously treated by platinum‑based chemotherapy. MATERIALS AND METHODS: We reviewed the hospital database and finally included 26 recurrent ovarian cancer patients who were treated with bevacizumab combined with gemcibabine or paclitaxel or single agent. All included patients received >3 cycle of bevacizumab treatment. The tumor response, overall survival, and toxicities were documented. RESULTS: Under the treatment of bevacizumab combined with gemcibabine or paclitaxel, 2 complete response (7.7%), 8 partial response (30.8%), 7 stable disease (26.9%) and 9 progression disease (34.6%) was documented with the objective response rate of 38.5% and disease control rate of 65.4%. The median overall survival from the first application of bevacizumab was 15.3 months [Figure 1] for all of the 26 patients. The median overall survival time was 16.2 and 14.0 months for bevacizumab + gemcitabine and bevacizumab + paclitaxel treatment schedule respectively. The overall survival was not different between bevacizumab + gemcitabine and bevacizumab + paclitaxel treatment regimen hazard ratio = 0.80 (95% confidence interval: 0.32–2, P = 0.64). The hypertension and proteinuria were the major bevacizumab related toxicities. CONCLUSIONS: Bevacizumab combined with gemcibabine or paclitaxel was a promising treatment schedule for platinum‑resistance recurrent ovarian cancer.
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Objective To investigate the relationship between the expression of BRCA1,β-tubulin III (TUBB3) and their efficacies with platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods The expression levels of BRCA1 and TUBB3 were detected by immunohistochemistry. The relationship between BRCA1 and TUBB3 expressions and their efficacies were analyzed. Results The high expression rate of BRCA1 was 34.8%, and the efficacy of platinum-based chemotherapy in patients with BRCA1-lower expression is obviously better than that in patients with BRCA1-higher expression. There was a significant difference between these two groups (30.4%vs 67.4%, P=0.004). The effective rate of platinum-based chemotherapy in TUBB3-higher expression group and TUBB3-lower expression group were illustrated no significance (59.4% vs 50.0%, P=0.445). Conclusion Platinum-based chemotherapy is more suitable for the advanced NSCLC patients with lower expression of BRCA1. The expression level of BRCA1 could be used to predict the efficacy of platinum-based chemotherapy in advanced NSCLC patients.
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Objective: This study aims to observe the efficacy and toxicity of three-dimensional conformal radiotherapy (3DCRT) combined with weekly topotecan hydrochloride (Top-Hyd) chemotherapy on patients with platinum-resistant recurrent ovarian cancer. Methods: Medical data of 42 patients with platinum-resistant recurrent ovarian cancer between June 2008 and June 2011 were retrospectively reviewed. OAOf these 42 patients, 22 underwent 3DCRT combined with weekly Top–Hyd chemotherapy, whereas the remaining 20 underwent simple chemotherapy (SCT). Doses from 45 Gy to 65 Gy were planned to deliver fractions ranging from 1.8 Gy to 2 Gy to patient abdomen and pelvis. Top–Hyd (4 mg/m2) was aintravenously administered 1, 8, and 15 days from radiotherapy, with a cycle of 28 days. Results: By December 31, 2011, the median follow-up time for the 3DRT group was 18.5 months, whereas that for the SCT group was 10.8 months . The total response rate and the clinical beneficial rate were significantly higher in the 3DCRT group than in the SCT group (total response rate, 42.1% vs. 11.1%; clinical beneficial rate, 68.4% vs 22.2% at P0.05). Conclusion: The combined 3DCRT treatment and Top-Hyd chemotherapy results in enhanced response and tolerable toxicity compared with SCT in patients with recurrent ovarian cancer infiltrating the pelvic and retroperitoneal lymph node metastasis. So, it may be the salvage regimen for recurrent ovarian cancer and provide a new therapeutic option for the consolidation treatment of advanced ovarian carcinoma.