Efficacy and safety of endostar combined with chemoradiotherapy versus chemoradiotherapy alone in locally advanced cervical cancer: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: To evaluate the role and safety of endostar in cervical cancer by comparing the efficacy and adverse reactions of endostar combined with concurrent chemoradiotherapy in patients with locally advanced cervical carcinoma. METHODS: The quality of the included literature was evaluated by searching the database for the comparison of endostar combined with concurrent radiotherapy and chemotherapy in cervical cancer patients; objective response rate (ORR) and disease control rate (DCR) were used as the main outcome indicators, and statistical analysis was performed using RevMan5.3 and State15.3 software. RESULTS: A total of 13 studies were included in this study, including 1057 patients with locally advanced cervical cancer, suggesting that endostar combined with chemoradiotherapy can significantly improve the objective response rate (ORR: odds ratio 3.88, 95% confidence interval 2.77-5.45, P < .00001) and disease control rate (DCR: odds ratio 4.43, 95% confidence interval 2.78-7.04; P < .00001), and there was no significant increase in treatment-related adverse reactions. CONCLUSIONS: In this meta-analysis, endostar combined with concurrent chemoradiotherapy significantly improved ORR and DCR in patients with locally advanced cervical cancer without increasing toxicity. However, this study only analyzed the short-term efficacy of endostar, and its influence on overall survival and progression-free survival needs to be further verified in large randomized controlled trials with long-term follow-up.

COQ10B Knockdown Modulates Cell Proliferation, Invasion, Migration, and Apoptosis in Esophageal Squamous Cell Carcinoma.

Objective: Esophageal squamous-cell carcinoma (ESCC) is an aggressive malignant tumor, accounting for more than 90% of esophageal cancers. However, treatments such as surgical resection, radiotherapy, and chemotherapy are unable to achieve ideal clinical outcomes. The purpose of this study was to explore the effects of COQ10B on proliferation, apoptosis, migration, and invasion of esophageal squamous-cell carcinoma (ESCC) cells. Methods: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of COQ10B in ESCC and normal tissues and in ESCC cell lines (KYSE-15 and TE-1). MTT assay and flow cytometry were applied to investigate the effects of COQ10B shRNA lentivirus (LV-shCOQ10B) on ESCC cell proliferation and apoptosis, respectively. The effect of COQ10B silencing on ESCC cell migration and invasion was determined by wound healing assay and transwell invasion assay, respectively. Results: The expression of COQ10B mRNA in ESCC tissues was higher than that in surrounding tissues. The decreased COQ10B level in KYSE-15 and TE-1 cells by LV-shCOQ10B could inhibit cell proliferation, promote cell apoptosis, and reduce the ability of invasion and migration (all P < 0.05). Conclusion: COQ10B was highly expressed in human ESCC tissues. COQ10B silencing contributed to the inhibition of proliferation, invasion, and migration of ESCC cells and the promotion of cell apoptosis, suggesting COQ10B may be a potential molecular target for the diagnosis and treatment of ESCC.

Integrin-linked kinase affects the sensitivity of esophageal squamous cell carcinoma cells to chemotherapy with cisplatin via the Wnt/beta-catenin signaling pathway.

Recent studies have shown that the expression of integrin-linked kinase (ILK) was related to the occurrence, development, and malignant progression of esophageal squamous cell carcinoma (ESCC). However, research on the relationship between ILK and the chemosensitivity of ESCC has to date not been reported. The present study found that ILK was highly expressed in ESCC cell lines, and the overexpression of ILK in ESCC cells reduced the incidence of cell apoptosis and alleviated the cytotoxicity on cells induced by cisplatin (CDDP). Inversely, ILK knockdown increased CDDP-induced apoptosis and had an inhibitive effect on the malignant phenotype of ESCC, including cell proliferation, invasion, and migration. In addition, ILK knockdown in ESCC cells inhibited the expression of beta (ß)-catenin and activated the wingless/integrated (Wnt) signaling pathway. Furthermore, cellular MYC (c-MYC) and Cylin D1 were the target genes of the Wnt signaling pathway. Rescue experiments showed that the overexpression of ß-catenin reversed a tumor's inhibition and apoptosis abilities induced by ILK knockdown. In conclusion, ILK potentially reduced the CDDP sensitivity of ESCC cells by influencing the activity of the Wnt/ß-catenin signaling pathway.

Computational Drug Repurposing Approach to Identify Novel Inhibitors of ILK Protein for Treatment of Esophageal Squamous Cell Carcinoma.

Purpose: Esophageal squamous cell cancer (ESCC) is a deadly malignant tumor characterized by an overall 5-year survival rate below 20%, with China accounting for approximately 50% of all cases worldwide. Our previous studies have demonstrated that high integrin-linked kinase (ILK) expression plays a key role in development and progression of ESCC both in vitro and in vivo. Here, we employed the drug repurposing approach to identify a novel FDA-approved anticancer inhibitor against ILK-induced tumorigenesis and progression. Methods: We screened the ZINC15 database and predicted the molecular docking ability among FDA-approved and publicly available drugs to ILK and then performed computational docking and visual inspection analyses of the top 10 ranked drugs. Two computer-based virtual screened drugs were evaluated in vitro for their ability to directly bind purified ILK by surface plasmon resonance. Cytotoxicity of the two candidate drugs was validated in vitro using CCK-8 and LDH assays. Results: We initially selected the top 10 compounds, based on their minimum binding energy to the ILK crystal, after molecular docking and subjected them to further screening. Taking the binding energy of -10 kcal/mol as the threshold, we selected two drugs, namely, nilotinib and teniposide, for the wet-lab experiment. Surface plasmon resonance (SPR) revealed that nilotinib and teniposide had equilibrium dissociation constant (KD) values of 6.410E - 6 and 1.793E - 6, respectively, which were lower than 2.643E - 6 observed in ILK-IN-3 used as the positive control. The IC50 values for nilotinib and teniposide in ESCC cell lines were 40 µM and 200-400 nM, respectively. Results of the CCK-8 assay demonstrated that both nilotinib and teniposide significantly inhibited proliferation of cells (P < 0.01). LDH results revealed that both drugs significantly suppressed the rate of cell death (P < 0.01). Conclusion: The drug repositioning procedure can effectively identify new therapeutic tools for ESCC. Our findings suggest that nilotinib and teniposide are efficacious inhibitors of ILK and thus have potential to target ILK-mediated signaling pathways for management of ESCC.

Efficacy and safety of single-agent PD-1 inhibitors versus chemotherapy in second-line treatment of advanced esophageal squamous cell carcinoma: a Meta-analysis / 中国肿瘤生物治疗杂志

@# [摘 要] 目的：系统评价单药程序性死亡受体1（PD-1）抑制剂对比化疗二线治疗晚期食管鳞状细胞癌（ESCC）患者的疗效及安全性，以期为临床决策提供最佳循证医学证据。方法：计算机检索The Cochrane Library、Web of Science、PubMed、EMbase、CNKI和万方等数据库，同时检索J Clin Oncol、N England Oncol、Lancet Oncol等杂志以及ASCO、EMSO会议摘要中有关单药PD-1抑制剂对比传统化疗二线治疗晚期ESCC患者的临床随机对照试验（RCT），筛选文献，提取资料，采用RevMan5.3进行Meta分析。结果：共纳入5项RCT研究（1 732例患者）。与化疗组比，单药PD-1抑制剂二线治疗晚期ESCC可显著延长患者的总生存期（OS）（HR＝0.75，95% CI：0.67~0.83，P<0.000 01）。以PD-L1不同表达程度进行亚组分析，在延长OS方面，TPS<1%时，单药PD-1抑制剂二线治疗晚期ESCC无明显优势；而TPS≥1%、TPS<5%、TPS≥5%、TPS<10%、TPS≥10%时，单药PD-1抑制剂二线治疗均可显著延长晚期ESCC患者的OS，且PD-L1表达程度越高，疗效获益更显著。然而，与化疗组比，单药PD-1抑制剂在延长晚期ESCC患者的无进展生存期（PFS）（HR＝0.93，95% CI：0.79~1.10，P=0.41）及提高客观有效率（ORR）（RR＝1.62，95% CI：0.95~2.74，P=0.07）等方面，差异均无统计学意义。但单药PD-1抑制剂组3~5级不良反应发生率低（RR＝0.37，95% CI：0.28~0.50，P<0.000 01）。结论：单药PD-1抑制剂二线治疗晚期ESCC患者可显著延长患者的OS；PD-L1高表达者PD-1抑制剂可作为二线治疗的优先选择，且具有良好的安全性。 , , , , , ()

Expression of integrin-lined kinase in esophageal squamous cell carcinoma tissues and its effect on proliferation and apoptosis of KYSE-150 cells and the growth of xenografts in nude mice / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：分析整合素连接激酶（ILK）基因在食管鳞状细胞癌（ESCC）组织中的表达水平及其与患者临床病理特征之间的关系，探讨其对KYSE-150细胞增殖、凋亡和裸鼠皮下移植瘤生长的影响。方法:选取2012年1月至2014年12月手术切除并经病理证实的75例ESCC患者的癌组织和其配对的癌旁组织标本，用组织芯片技术及免疫组织化学染色法检测ESCC组织和癌旁组织中ILK的表达情况；qPCR法检测ESCC细胞ECA109、TE-1、EC9706、KYSE-150中ILK mRNA的表达，选用ILK表达最高的KYSE-150细胞进行后续细胞功能学研究。使用ILK干扰慢病毒感染KYSE-150细胞下调ILK的表达，qPCR和WB法检测ILK基因敲降效率；MTT实验、克隆形成实验和FACS检测干扰ILK表达对KYSE-150细胞增殖能力和凋亡水平的影响；裸鼠皮下成瘤实验检测干扰ILK对KYSE-150细胞移植瘤生长的影响。结果:ESCC组织中ILK蛋白阳性表达率高于癌旁组织（P<0.05），且ILK高表达与淋巴结转移有关联（P<0.05）。ILK干扰慢病毒感染的KYSE-150细胞中ILK mRNA表达明显受到抑制（P<0.05），ILK蛋白水平表达下调，以上结果提示ILK敲降成功。与感染阴性对照病毒的KYSE-150细胞相比，ILK干扰慢病毒感染的KYSE-150细胞的增殖能力、克隆形成数均显著降低（均P<0.05），但细胞凋亡率升高（P<0.05）。与对照组相比，干预组裸鼠移植瘤生长缓慢，移植瘤的质量及体积均较小（均P<0.05）。结论:ESCC组织中ILK的表达高于癌旁组织，且ILK高表达与患者发生淋巴结转移有关联；抑制ILK基因可导致KYSE-150细胞增殖能力降低，促进细胞凋亡而抑制裸鼠移植瘤生长。

ILK predicts the efficacy of chemoradiotherapy and the prognosis of patients with esophageal squamous cell carcinoma.

Isobaric tags for relative and absolute quantitation (iTRAQ) technology was adopted to screen differentially-expressed proteins in the serum that predict the effects of chemoradiotherapy on esophageal squamous cell carcinoma (ESCC). Thus, significantly related proteins can be functionally identified at the cellular level. A total of 60 patients diagnosed with locally advanced and advanced ESCC were recruited and treated with chemoradiotherapy. The iTRAQ technique was used to screen serum differentially expressed proteins associated with chemoradiotherapeutic efficacy. Functional identification of significantly related proteins was performed at the cellular level. Cell proliferation was detected using MTT, clonogenic and fluorescence assays, and apoptosis was assessed using flow cytometry. Transwell and wound-healing assays were used to detect the invasion and migration properties of cancer cells. Proteomics results revealed that prior to chemoradiotherapy, the expression level of integrin-linked kinase (ILK) was significantly upregulated in patients with ESCC, compared with that of the control group [ratio (r)=4.386; P<0.05], and significantly downregulated in the chemoradiotherapy-sensitive group, compared with the chemoradiotherapy-resistant group (r=0.587; P<0.05). At the cellular level, the proliferation rate of cells in the experimental group was significantly inhibited (P<0.05), and the number of cell colonies was decreased (P<0.01), while the number of apoptotic cells was significantly increased (P<0.01). The invasive ability of TE-1 cells in the shILK group was significantly inhibited (P<0.01), and the migration rate was significantly retarded at 8 and 24 h (P<0.01). The present study highlighted the potential value of ILK in predicting the efficacy of chemoradiotherapeutic treatment in patients with ESCC, and that ILK gene-silencing inhibits the progression of ESCC.

Efficacy and safety of ramucircumab in treatment of advanced non-small cell lung cancer：a Meta analysis / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To systematically evaluate the efficacy and safety of ramcircumab in the treatment of advanced non-small cell lung cancer (NSCLC) by a Meta-analysis. Methods: The randomized controlled clinical trials of ramcircumab in the treatment of advanced non-small cell lung cancer were retrieved from Cochrane Library (2017, Issue 8), Web of Science, Pubmed, EMbase, Wanfang Database, CNKI, CBM, Chinese Science and TechnologyAcademic Journal andASCO, ESMO main conference database, with the enddate of September 1, 2017. Two independent reviewers selected the literatures, extracted the data, and assessed the quality of the included studies. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse reactions in NSCLC patients of ramcircumab group and control group were analyzed by RevMan5.3 software. Results: Three RCTs were finally included in this meta-analysis. A total of 1 545 NSCLC patients were enrolled, including 777 in ramcircumab group and 768 in control group. The PFS and OS of NSCLC patients in the ramcircumab group were all better than those of the control group (HR=0.77,95%CI[0.69-0.85], P<0.01; HR=0.88, 95%CI[0.78-0.99], P<0.05). However, there was no statistically significant difference in the ORR between the ramcircumab group and the control group (RR=1.33, 95%CI[0.68-2.61], P>0.05). Compared with docetaxel single-agent second-line treatment, Ramcircumab combined with docetaxel can prolong PFS and OS of advanced NSCLC patients (HR=0.77, 95%CI[0.69-0.86], P< 0.01; HR=0.86, 95%CI [0.76-0.98], P<0.05). The most serious adverse reaction in the ramcircumab group was hypertension (RR=3.33, 95%CI[1.83-6.05], P<0.01); whereas the incidences of nausea, vomiting, diarrhea, loss of appetite, fatigue, proteinuria, neutropenia, leukopenia, thrombocytopenia, and bleeding etc. showed no significant differences between the two groups (all P>0.05). Conclusion: Ramcircumab can prolong PFS and OS of patients with advanced NSCLC. The main adverse reaction is hypertension.