Survivin-D53A (SVV-D53A) is a dominant-negative mutant survivin, which represents a potential promising target for cancer gene therapy. The present study was designed to determine whether SVV-D53A plasmid encapsuled by DOTAP: Chol liposome would have the anti-tumor activity against SPC-A1 lung adenocarcinoma, and to detect the possible mechanisms. In our experiment, SPC-A1 cells were transfected in vitro with SVV-D53A plasmid and examined for protein expression by Western blot, then flow cytometric analysis was used to detect apoptosis. SPC-A1 lung adenocarcinoma xenografts were established in vivo in the nude mice, which received the i.v. administrations of SVV-D53A plasmid/liposome complexes. After mice were sacrificed, the paraffin-embedded tumor tissue sections were used for proliferating cell nuclear antigen (PCNA) expression and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)assay. Compared with the control group, the mice treated with SVV-D53A plasmid had an obviously reduced tumor volume, with high level of apoptosis and decreased cell proliferation in tumor tissue. The research results proved that the administration of SVV-D53A plasmid resulted in significant inhibition of SPC-A1 cells both in vitro and in vivo. The functional mechanism is that the anti-tumor response causes and induces tumor cell apoptosis.
【摘要】 目的 评价伴骨转移的非小细胞肺癌（non-small cell lung cancer，NSCLC）患者在接受帕米膦酸二钠和唑来膦酸治疗后的有效性和安全性。 方法 2007年6月-2008年12月，74例伴骨转移的NSCLC，患者接受了双膦酸盐治疗，其中50例接受帕米膦酸二钠治疗，24例接受唑来膦酸治疗。帕米膦酸二钠90 mg，静脉滴注3 h，每4周重复1次；唑来膦酸4 mg，静脉滴注15 min，每4周重复1次。对可能影响其骨相关事件发生时间及生存率的各种临床﹑病理、治疗方法等因素进行分析，用Kaplan-Meier曲线及Log rank检验生存率差异，对不良反应的发生率等采用χ2检验。 结果 18个月无骨相关事件生存率和总体生存率在帕米膦酸二钠及唑来膦酸组分别为19.3%、28.9%（P=0.253）和33.4%、38.2%（P=0.745），两组比较，差异均无统计学意义。两组患者不良反应中帕米膦酸二钠组8例（16.0%），唑来膦酸组6例（25.0%），两组比较差异无统计学意义（χ2=0.200，P=0.655）。7例患者用帕米膦酸二钠治疗失败后再用唑来膦酸治疗，其中位无骨相关事件生存时间为2个月（95%CI：0~4.6）。 结论 唑来膦酸和帕米膦酸二钠在缓解延迟骨相关事件发生时间疗效和不良反应发生率相当。用帕米膦酸二钠治疗失败后再用唑来膦酸可延缓骨相关事件发生时间。【Abstract】 Objective To retrospectively evaluate the efficacy and safety of pamidronate disoclium and zoledronic acid in treating non-small-cell lung cancer (NSCLC) patients with bone metastasis. Methods This study included 74 patients who were treated with bisphosphonate between June 2007 and December 2008. Fifty were treated with pamidronate disodium, and 24 with zoledronic acid. Pamidronate disodium was administered intravenously once for 3 hours every 4 weeks at a dose of 90 mg. Zoledronic acid was given intravenously once for 15 minutes every 4 weeks at a dose of 4 mg. Various clinical, pathological factors and treatment methods related to the occurring time of skeletal related events (SRE) and survival rate were analyzed. Kaplan-Meier curve and Log rank were adopted to detect the difference in survival rate between patients treated with different medicine, and we used χ2 test to discover the rate of adverse events of the patients. Results Eighteen-month SRE-free survival and overall survival rate in the pamidronate disodium and zoledronic acid group were 19.3% vs. 28.9% (P=0.253), and 33.4% vs. 38.2% (P=0.745) respectively. There were 8 (8/50) cases of adverse events in the pamidronate disodium group, and 6 (6/24) in the zoledronic acid group (χ2=0.200, P=0.655). The SRE-free survival time for seven patients who were treated with zoledronic acid after pamidronate disodium failed was 2 months (95%CI: 0-4.6). Conclusions Compared with zoledronic acid, pamidronate has equal efficacy in delaying SRE and incidence of adverse effects. Administering zoledronic acid after pamidronate failed can also delay the occurring time of SRE.
ObjectiveTo explore the therapeutic efficacy of crizotinib for patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). MethodsWe retrospectively analyzed the clinical data of 31 ALK-positive NSCLC patients who received crizotinib treatment between November 2012 and May 2014 in the Department of Thoracic Oncology of West China Hospital. The median age of the patients was 51 years old, and the percentage of male and female patients was 45.2% and 54.8%, respectively. Among them, 74.2% were non-smokers, 74.2% had an ECOG performance status of 0-2. Histologically, adenocarcinoma was the highest proportion of 96.8%, and one (3.2%) patient had large cell carcinoma. Fifteen (48.4%) ALK-positive patients were given crizotinib in the first-line setting, and 16 (51.6%) accepted crizotinib in the second-line and beyond. ResultsThe objective response rate (ORR) of the patients treated with crizotinib was 61.3%, and the disease control rate (DCR) was 90.3%. The median progression-free survival (time) was 10.0 months [(95% CI (2.9, 17.0) months]. The difference of ORR and DCR between the patients given crizotinib in the first-line setting and the patients given crizotinib in the second-line or beyond was not statistically significant (P=0.716 and P=0.600, respectively). The most frequent treatment-related adverse events were increased aspartate aminotransferase/alanine aminotransferase (64.5%), nausea and vomiting (35.5%), leukopenia (16.7%), vision disorder (16.1%), edema (12.9%), and diarrhea (12.9%), and most toxicities were grade 1 and 2. ConclusionThis study shows that crizotinib can increase the objective response rate and disease control rate, prolong progression-free survival time in patients with advanced ALK-positive non–small-cell lung cancer. Crizotinib has relative fewer side effects and can be tolerated by the patients.
Objective To investigate the clinical features of non-small cell lung cancer (NSCLC) patients with long-term survival and the related factors for treatment. Methods A retrospective analysis of clinical features, treatment factors, and survival was performed for 963 patients with pathologically confirmed stage Ⅳ NSCLC between January 2010 and December 2015 from Department of Thoracic Oncology, West China Hospital, Sichuan University. Results The median overall survival (OS) of the 963 patients was 20.8 months, and the 1-, 3-, 5-, and 7-year survival rates were 72.0%, 21.4%, 15.2%, and 4.8%, respectively. There were 81 patients in the long-term survival group (OS>60 months) and 882 in the non-long-term survival group (OS<60 months). Previous surgery, thoracic radiotherapy and epidermal growth factor receptor (EGFR) gene positive significantly increased the 5-year actual survival rate, reducing the risk of death by 62.0%, 58.8%, and 58.1%, respectively. Compared with the non-long-term survival group, more patients in the long-term survival group received two or more means of treatment including surgery, thoracic radiotherapy, and targeted therapy (28.4% vs. 11.6%, P<0.001) and more patients benefited from fourth- or further-line treatment (24.7%vs. 11.1%, P<0.001). Cox multivariate regression analysis indicated that performance status [hazard ratio (HR)=1.388, 95% confidence interval (CI) (1.199, 1.608), P<0.001] , N stage [HR=1.160, 95%CI (1.058, 1.272), P=0.002] , EGFR gene status [HR=0.588, 95%CI (0.469, 0.738), P<0.001] , previous surgery [HR=0.626, 95%CI (0.471, 0.832), P=0.001] , and thoracic radiotherapy [HR=0.592, 95%CI (0.480, 0.730), P<0.001] were independent prognostic factors of OS. Conclusions Good performance status, early N staging, EGFR mutation, previous surgery, and thoracic radiotherapy are important prognostic factors affecting the survival of advanced NSCLC patients. Long-term survival benefits from combined treatment and effective further-line therapies.