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。

Rare type I CBFβ/MYH11 fusion transcript in primary acute myeloid leukemia with inv(16)(p13.1q22): a case report

Inv(16)(p13.1q22) in acute myeloid leukemia (AML) is a common chromosomal abnormality. It leads to the core-binding factor ß-subunit (CBFβ)/smooth muscle myosin heavy chain 11 (MYH11) fusion gene. Different breakpoints were observed in the CBFβ gene at 16q22 and the MYH11 gene at 16p13.1. For this reason, different CBFβ/MYH11 fusion genes are generated, with more than 13 types having been reported to date. Type I CBFβ/MYH11 fusion transcripts are very rare, with only 10 cases being reported to date. This case report describes a primary AML patient with inv(16)(p13.1q22) and a rare type I CBFβ/MYH11 fusion gene. The morphological analysis did not conform to the typical M4eo. Abnormal eosinophils were less than 5%, and there was obvious dysgranulopoiesis. The patient was in hematological and genetic remission for 487 days after the initial chemotherapy cycles. However, the CBFβ/MYH11 fusion had been constantly positive. Moreover, the presence of non-type A fusions may affect its biology and clinical prognosis. Therefore, further studies on understanding its biological and prognostic significance are essential.

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.

Insulin-like growth factor binding protein-3 interacts with the thyroid hormone receptor α1 and modulates transcription of thyroid hormone responsive gene / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the interaction between insulin-like growth factor binding protein-3 (IGFBP-3) and thyroid hormone receptor α1 (TRα1) and the modulatory effect of IGFBP-3 on transcription of the thyroid hormone responsive gene.</p><p><b>METHODS</b>The interaction between IGFBP-3 and TRα1 was detected with glutathione-S-transferase pull-down method, co-immunoprecipitation, fluorescence resonance energy transfer test. The cellular distribution of these two proteins was observed by confocal laser scanning microscopy. The effect of IGFBP-3 on the growth hormone promoter activity stimulated by triiodothyronine (T3) was determined by dual-luciferase reporter assay.</p><p><b>RESULTS</b>IGFBP-3 interacted with TRα1 both in vivo and in vitro. IGFBP-3 and TRα1 were shown to co-localize in the nucleus of HEK-293 cells. The overexpressed IGFBP-3 inhibited the growth hormone promoter activity stimulated by T3 (P<0.01).</p><p><b>CONCLUSIONS</b>IGFBP-3 interacts with TRα1 and inhibits T3 responsive gene transcription. This finding further confirms the insulin-like growth factor-independent role of IGFBP-3 in the nucleus.</p>