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Kanglaite injection plus platinum-based chemotherapy for stage III/IV non-small cell lung cancer: A meta-analysis of 27 RCTs.

康莱特注射液联合铂类化疗治疗 ⅲ/ⅳ 期非小细胞肺癌: 27 项rct的荟萃分析。

  • 影响因子:4.09
  • DOI:10.1016/j.phymed.2019.153154
  • 作者列表:"Huang X","Wang J","Lin W","Zhang N","Du J","Long Z","Yang Y","Zheng B","Zhong F","Wu Q","Ma W
  • 发表时间:2020-02-01

BACKGROUND:Kanglaite injection (KLT) is a broad-spectrum anti-tumor drug, which is extracted from the seeds of the Chinese medicinal herb Coix lacryma-jobi, and has been widely used for the treatment of advanced lung cancer. PURPOSE:To evaluate the combined effects of Kanglaite injection plus platinum-based chemotherapy (PBC) on patients with stage III/IV non-small cell lung cancer (NSCLC). STUDY DESIGN:A systematic review and meta-analysis of randomized clinical trials (RCTs). MATERIALS AND METHODS:Twelve databases were searched from their inceptions until July 05, 2019. All the RCTs comparing the efficacy and safety of Kanglaite injection plus PBC versus PBC alone were selected. Analyses were performed using Review Manager 5.3, Comprehensive Meta-Analysis 3.0 and Trial Sequential Analysis (TSA). Disease control rate (DCR) was defined as the primary endpoint, objective response rate (ORR), survival rate, quality of life (QOL), cellular immunity function, and toxicities were defined as the secondary endpoints. RESULTS:Twenty-seven RCTs recruiting 2,243 patients with stage III/IV NSCLC were included. The results showed that, compared with PBC alone, Kanglaite injection plus PBC improved DCR (RR = 1.20, 95% CI 1.15-1.26, p < 0.00001), ORR (RR = 1.45, 95% CI 1.31-1.60, p < 0.00001), 1-year survival rate (RR = 1.20, 95% CI 1.02-1.43, p = 0.03), QOL (RR = 1.32, 95% CI 1.25-1.40, p < 0.00001), CD4+T cells (WMD = 4.86, 95% CI 4.00-5.73, p < 0.00001), CD4+/CD8+ ratio (WMD = 0.19, 95% CI 0.07-0.31, p < 0.002), and reduced severe toxicities by 59% (RR = 0.41, 95% CI 0.33-0.51, p < 0.00001). Most results were robust and the quality of evidence was from moderate to low. CONCLUSIONS:Kanglaite injection in combination with PBC showed significantly higher efficacy than PBC alone in the treatment of stage III/IV NSCLC. Moreover, the combination therapy can improve cellular immunity and attenuate the severe toxicities caused by chemotherapy. However, high-quality RCTs are warranted to further assess the effects of the combined therapy.


背景: 康莱特注射液是从中药薏苡仁中提取的一种广谱抗肿瘤药物,并已广泛用于晚期肺癌的治疗。 目的: 评价康莱特注射液联合铂类化疗 (PBC) 治疗 ⅲ/ⅳ 期非小细胞肺癌 (NSCLC) 的疗效。 研究设计: 随机临床试验 (RCTs) 的系统评价和荟萃分析。 材料和方法: 从 12 个数据库中检索到 2019 年 7 月 5 日。选择比较康莱特注射液联合PBC与单纯PBC疗效和安全性的所有rct。使用Review Manager 5.3,全面荟萃分析 3.0 和试验序贯分析 (TSA) 进行分析。疾病控制率 (DCR) 定义为主要终点、客观缓解率 (ORR) 、生存率、生活质量 (QOL) 、细胞免疫功能、和毒性被定义为次要终点。 结果: 纳入了 27 项rct,招募了 2,243 例III/IV期NSCLC患者。结果显示,与单纯PBC相比,康莱特注射液联合PBC改善DCR (RR = 1.20,95% CI 1.15-1.26,p <0.00001),ORR (RR = 1.45,95% CI 1.31-1.60,p <0.00001) 、 1 年生存率 (RR = 1.20,95% CI 1.02-1.43,p = 0.03) 、QOL (RR = 1.32,95% CI 1.25-1.40,p <0.00001),CD4 + T细胞 (WMD = 4.86,95% CI 4.00-5.73,p <0.00001),CD4 +/CD8 + 比值 (WMD = 0.19,95% CI 0.07-0.31,p <0.002),严重毒性降低 59% (RR = 0.41,95% CI 0.33-0.51,P <0.00001)。大多数结果是稳健的,证据质量从中等到低。 结论: 康莱特注射液联合PBC治疗 ⅲ/ⅳ 期NSCLC的疗效明显优于单纯PBC。此外,联合治疗可以提高细胞免疫,减轻化疗引起的严重毒性。然而,需要高质量的rct来进一步评估联合治疗的效果。



作者列表:["Mammana M","Zuin A","Serra E","Bellini A","Rea F"]

METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

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作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

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作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

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