Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the development and use of several targeting drugs for lung cancer therapy, the five-year survival rate has remained as low as 15% for the past three decades. Cisplatin-based chemotherapy is considered the first-line therapeutic strategy for lung cancer. However, developments of chemoresistance is a major obstacle for the successful treatment. Therefore, the development of novel therapy against cisplatin-resistance lung cancer is imperative. Photodynamic therapy (PDT), which is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS) and oxygen, may provide an unprecedented tool to develop more effective treatments. To provide experimental basis for its application in cisplatin-resistance lung cancer, we will discuss the biological effects of MPPa-photodynamic therapy in human cisplatin-resistance lung cancer cells in this article. Human cisplatin-resistance lung cancer cells A549/DDP were co-cultured with MPPa (0, 1, 2, 4, 8, 16 μmol/L) and exposed to light (0, 0.6, 1.2, 2.4, 3.6, 4.8 J/cm2), and cell viability was determined with CCK-8 assay. Flow cytometry was used to detect apoptosis, DCFH-DA staining was employed to observe reactive oxygen species (ROS), and Western blot was used to detect the expressions of B-cell lymphoma-2 (Bcl-2) protein and Bcl-2 associated X protein (Bax). The proliferation of A549/DDP cells was suppressed by PDT. The apop-totic rate in the PDT group was significantly higher than that in the control, MPPa or light group (P < 0.05). The level of ROS was increased. The expression of Bax was increased, and that of Bcl-2 was decreased. MPPa-photodynamic therapy can significantly suppress cell viability, and induce apoptosis in human cisplatin-resistance lung cancer cells.
Objective To evaluate the effectiveness and safety of nedaplatin combined with chemotherapy versus cisplatin combined with chemotherapy for advanced non-small cell lung cancer (NSCLC). Methods The randomized controlled trials (RCTs) on nedaplatin combined with chemotherapy versus cisplatin combined with chemotherapy for advanced NSCLC were searched in The Cochrane Library, PubMed, EMbase, CBM, VIP and WanFang Data from the date of their establishment to January 2012. According to the inclusion and exclusion criteria, two reviewers independently screened the studies, extracted the data and assessed the quality. Then RevMan 5.0 software was used for meta-analysis. Results A total of 15 RCTs involving 1 076 patients were included. The results of meta-analysis showed that, compared with the cisplatin combined with chemotherapy, nedaplatin combined with chemotherapy could reduce the risks of nausea and vomiting (RR=0.56, 95%CI 0.48 to 0.65, Plt;0.000 01), decrease the risk of renal function impairment (RR=0.47, 95%CI 0.30 to 0.74, P=0.001), but increase the risk of thrombocytopenia (RR=1.59, 95%CI 1.20 to 2.11, P=0.001). There were no significant differences between the two groups in objective response rate (ORR) (RR=1.09, 95%CI 0.92 to 1.29, P=0.03), leukopenia (RR=1.05, 95%CI 0.92 to 1.19, P=0.50), and hemoglobin reduction (RR=0.92, 95%CI 0.80 to 1.07, P=0.30). Conclusion Compared with cisplatin combined with chemotherapy for advanced NSCLC patients, nedaplatin in combination with chemotherapy can significantly reduce the risks of nausea, vomiting and renal function impairment. Although the ORRs are similar in the two groups, nedaplatin combined with chemotherapy can cause a higher risk of thrombocytopenia. For the quality restriction and possible publication bias of the included studies, more high quality RCTs are required to further verify this conclusion.
ObjectiveTo systematically review the efficacy and safety of intrapleural injection of endostar combined with cisplatin in treatment of non-small cell lung cancer (NSCLC) with malignant pleural effusion. MethodsDatabases including PubMed, The Cochrane Library (Issue 2, 2016), EMbase, Web of Science, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials (RCTs) about endostar combined with cisplatin for NSCLC with malignant pleural effusion from inception to February 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. ResultsA total of 10 RCTs involving 610 patients were finally included. The results of meta-analysis showed that: The overall response rate and the improvement rate of quality of life in the endostar combined with cisplatin group were higher than that of the cisplatin alone group (RR=1.71, 95%CI 1.49 to 1.95, P<0.00001; RR=1.68, 95%CI 1.44 to 1.96, P<0.00001, respectively). However, There were no significant differences between two groups in incidence of gastrointestinal reaction, incidence of leucopenia and incidence of thrombocytopenia (all P values>0.05). ConclusionCompared with cisplatin, intrapleural injection of endostar combined with cisplatin can improve the overall response rate and improve the quality of life of NSCLC patients with malignant pleural effusion. Due to the limited quality and quantity of included studies, more high quality studies are needed to verify the above conclusion.
Forty-six patients with advanced gastric cancer were investigated. 25 patients were randomized to receive intraperitoneal hyperthermic (43℃) hypotonic perfusion with high dose cis-diamminedichloroplatinum (60-200mg/m2 body surface) and sodium thiosulfate intraveneously (7.5g/m2 body surface). The time of the intraperotineal perfusion was 30 minutes with the total volume of the perfusate of 2500-3000ml. 21 patients were only operated. The sex ,age macro-or microscopic serosal invasion, and histologic type of two groups were similar and comparatible. We found no cancer cell in nine paients with positive intraperitoneal free cancer cell in the treated group. The postoperative 1-year survival rate of patients in the treated group (96.00%) was significantly higher than that of the random control group (48.54%), Ｐ＜0.01. The postoperative 1 1/2year survival rate in the treated group (68.88%) was also higher than that of the control group (40.00%), however, with no significant difference (Ｐ＞0.05). No serious myelosuppression, kindley,liver, and peripheral nerve damage, and other complications were found. The results indicated that this therapy is reasonably safe and could be a prophylactic theapy for the peritoneal recurrence after radical gastrectomy, which should be further investigated.
目的:比较常规放射治疗与放射治疗同期合并顺铂(PDD)加卡培他滨(CAP)治疗局部晚期鼻咽癌的有效性,同时评价此联合方式的安全性。方法:从2003年2月至2005年11月,78例局部晚期鼻咽癌患者(Ⅲ、Ⅳa,92分期)随机分为两组,放化疗组在放疗的第1、4、7周均用PDD+CAP各化疗一周期,PDD:20mg/m2,静脉滴注,连用5天;CAP:1000mg/m2,每天2次,连用14天,休7天;21天为一周期。两组放疗方法相同:鼻咽原发灶采用60Co外照射,颈部淋巴结引流区采用60Co前切线照射加深部X线垂直照射,鼻咽部剂量为65～70 Gy／6.5～7周,颈淋巴结转移灶剂量为65～70 Gy／6.5～7周。结果:放化疗组及单放组治疗结束后3个月鼻咽部肿瘤完全消退率分别为89.7%,69.2%(P﹤0.05)。3年生存率分别为76.9%,53.8%(P﹤0.05)。结论:顺铂加卡培他滨方案联合放化疗治疗局部晚期鼻咽癌可改善患者的生存,毒副反应可耐受。
This study aims to explore the temporal pattern of DNA breaks induced by nanosecond electric pulses (nsEP) in cisplatin-sensitive and cisplatin-resistant human ovarian cancer cells. Human ovarian cancer cells A2780 (cisplatin-sensitive subline) and C30 (cisplatin-resistant subline) were exposed to nsEP. Sham exposed groups were shame exposed to nsEP. Cell viability was determined using CCK-8 assay after 0 h, 4 h, 8 h, 12 h and 24 h, respectively, and the percentage of dead cells was calculated. The DNA break was detected with the alkaline single cell gel electrophoresis (comet assay), and the 75th percentiles of TL (tail length), TM (tail moment) and OTM (Olive tail moment) were measured. Cell viability displayed an early decrease and late increase, with the valley value seen at 8 h. Percentages of cell death and comet-formed in A2780 cells were higher than those in C30 cells (P<0.05) at 8 h, respectively. TL, TM and OTM in C30 cells were less than those in A2780 cells (P<0.05). The percentage of comet-formed correlated with that of cell death in either A2780 (r=0.997, P<0.05) or C30 (r=0.998, P<0.05) cells. DNA breaks induced by nsEP in cisplatin-sensitive cells differred from that in resistant cells, and DNA break resulted in fraction of cell death.
Objectives To explore the effects of curcumin and cisplatin on A549 lung cancer cell invasion and metastasis, and explore the influence of the two drugs on matrix metalloproteinase 9 (MMP-9) and E-cadherin protein. Methods MTT assay was performed to detect the effects of curcumin, cisplatin alone and the combination on A549 lung cancer cell proliferation. Transwell assay was performed to detect the effects of curcumin, cisplatin alone and the combination on the invasion and metastasis of lung cancer cells. Western blot was used to detect the protein expression of MMP-9 and E-cadherin. Results The proliferation inhibition of A549 lung cancer cell rate in 5, 10, 20, 40 μmol/L of curcumin was 6.50%±1.06%, 11.70%±0.88%, 22.97%±0.82%, 27.93%±0.94%, respectively. Compared with control group, the proliferation inhibition rates in four different curcumin groups were significantly increased (all P<0.01). The differences in the proliferation inhibition rates among four different curcumin groups were statistically significant (allP<0.05). The proliferation inhibition rates of A549 lung cancer cell in 1, 2, 4 mg/L of cisplatin were 7.12%±0.86%, 20.07%±1.14%, 26.88%±0.51%, respectively. Compared with control group, the proliferation inhibition rates in three different cisplatin groups were significantly increased (allP<0.01). The differences in the proliferation inhibition rates among three different cisplatin groups were statistically significant (allP<0.01). The proliferation inhibition rates of A549 lung cancer cell in curcumin (20 μmol/L) combined with cisplatin (1, 2, 4 mg/L respectively) were 28.37%±0.57%, 39.72%±0.64%, 46.27%±0.86%, respectively. Compared with control group and curcumin or cisplatin used alone, the proliferation inhibition rates of three combined groups were significantly increased (allP<0.01). The invasion inhibition rates of A549 lung cancer cell in curcumin group (20 μmol/L), cisplatin group (2 mg/L) and combined group (curcumin 20 μmol/L plus cisplatin 2 mg/L) were 38.62%±0.23%, 36.52%±0.33%, 63.78%±0.59%, respectively. Compared with control group and curcumin or cisplatin used alone, the invasion inhibition rates of combined group were significantly increased (allP<0.01). The protein grey values for curcumin group (20 μmol/L), cisplatin group (2 mg/L) and combined group (curcumin 20 μmol/L plus cisplatin 2 mg/L) were 0.768±0.047, 0.654±0.104, 0.684±0.008, 0.444±0.104 (MMP-9) and 0.603±0.170, 0.792±0.050, 0.784±0.045, 0.879±0.110 (E-cadherin), respectively. Compared with control group and curcumin or cisplatin used alone, the protein grey values of combined group were significantly different (allP<0.01 orP<0.05). Conclusions Curcumin and cisplatin combination can inhibit the invasion and metastasis of lung cancer A549 cells. Its mechanism may be related to downregulating MMP-9 and upregulating E-cadherin.
Objective To observe the effect of cisplatin in bletilla hyacinthine particle chemotherapy combined with 125I brachytherapy on short-and long-term outcomes and the toxic and side effects in advanced gastric cancer. Methods One hundred seventy-six patients with stage Ⅱ or stage Ⅲ advanced gastric cancer underwent curative surgical resection were included in this study. They were randomly divided into brachytherapy and chemotherapy group (n=48), intraperitoneal chemotherapy group (n=32) and intravenous chemotherapy group (n=48), and other patients who abandoned radiotherapy and chemotherapy and signed informed consent form by themselves were considered as control group (n=48). The short-and long-term outcomes and the toxic and side effects were observed and the survival of all patients was analyzed by Kaplan-Meier method and Log-Rank test. Results For short-term outcomes, the total effective rate in 4 groups were 95.83%, 71.88%, 64.58% and 52.08% respectively, and the difference was significant (Plt;0.05). For long-term outcomes, the 3 -and 5-year mortality rate was 37.50% and 56.30%, and 5-year median survival time was (14±4.51) months (95%CI: 14.419-4.512) in brachytherapy and chemotherapy group patients. The 3- and 5-year mortality rate was 78.12%and 93.75%and 5year median survival time was (10.6±1.13) months (95%CI: 10.620-1.163) in intraperitoneal chemotherapy group patients. The 3-and 5-year mortality rate was 79.21%and 95.80%and 5-year median survival time was (11±3.10) months (95%CI: 11.130-3.162) in intravenous chemotherapy group patients. The 3-and 5-year mortality rate was 87.50%and 95.83% and 5-year median survival time was (9±2.30) months (95%CI: 10.024-1.180) in control group patients. Compared with the vein chemotherapy group, the short distance puts the chemotherapy group disgusting vomit, the marrow to suppress, the liver function harm, the kidney function harm formation rate to reduce obviously (Plt;0.05). Conclusion Cisplatin in bletilla hyacinthine particle chemotherapy combined with 125I brachytherapy can reduce the toxic and side effects of drugs and prolong survival time of patients with advanced gastric cancer.
ObjectiveTo investigate MUC1 over-expression on chemotherapy of 5-fluorouracil and cisplatin for esophageal cancer cells. MethodsMUC1 over-expression and stable silencing of MUC1 expression esophageal cancer cell lines were constructed. Xenograft model of esophageal cancer was established in nude mice. Cisplatin (8 mg/kg, day 1 and day 7)and 5-fluorouracil (20 mg/kg, day 1 to 6)were injected intraperitoneally. Tumor volume and body weight of nude mice were measured. Tumor growth curve and body weight curve were drawn, and tumor inhibitory rate was calculated. ResultsBoth cisplatin and 5-fluorouracil suppressed tumor growth of MUC1 over-expression esophageal cancer nude mice. Body weight and tumor volume of nude mice of cisplatin and 5-fluorouracil groups were significantly smaller than those of the control group (P < 0.05), and the inhibitory effects of cisplatin were significantly greater than those of 5-fluorouracil (P < 0.05). There was no significant inhibitory effect in stable silencing of MUC1 expression esophageal cancer nude mice. ConclusionBoth cisplatin and paclitaxel can suppress the growth of MUC1 over-expression esophageal cancer, and cisplatin has greater inhibitory effects than 5-fluorouracil in tumor volume and body weight of nude mice.
ObjectiveTo systematically review the efficacy and safety of cisplatin combined with etoposide versus other platinum combined with etoposide in the treatment of small cell lung cancer (SCLC). MethodsWe searched PubMed, The Cochrane Library (Issue 8, 2013), MEDLINE (Ovid), CNKI, VIP and WanFang Data to collect randomized controlled trials (RCTs) concerning the efficacy and safety of cisplatin combined with etoposide (the cisplatin group) versus other platinum combined with etoposide (the control group) for SCLC. The search was up to August 2013. Two reviewers screened literatures according to the inclusion and exclusion criteria, extracted data and assessed the methodological quality of included studies. And then, meta-analysis was performed by using RevMan 5.2 software. ResultsA total of 6 RCTs involving 684 patients were included. The results of meta-analysis showed that there were no significant differences in disease control rate (DCR) (RR=1.03, 95%CI 0.91 to 1.17, P=0.63), overall response rate (ORR) (RR=1.04, 95%CI 0.97 to 1.11, P=0.33), occurrence of leukocytopenia (RR=0.97, 95%CI 0.81 to 1.17, P=0.77), decreased hemoglobin (RR=0.89, 95%CI 0.61 to 1.31, P=0.56) between the cisplatin group and the control group. Occurrence of thrombocytopenia was lower (RR=0.49, 95%CI 0.38 to 0.63, P<0.000 01) while occurrence of nausea and vomiting was higher (RR=1.80, 95%CI 1.40 to 2.31, P<0.000 01) in the cisplatin group. ConclusionCurrent evidence shows that the clinical efficacy of cisplatin combined with etoposide for SCLC is equal to other platinum combined with etoposide, but it has a certain advantage in decreasing the aggregative rate of platelets, while the gastrointesnial reaction patients should avoid using cisplatin combined with etoposide.