炎症因子与肺癌研究进展

目的：总结分析炎症因子在肺部肿瘤患者血清中的表达水平及其与肺部肿瘤临床病理特征间的关系及相关性。方法：应用PubMed及CNKl期刊全文数据库检索系统,以“炎症、肿瘤和肺”为关键词,检索年限为1996—01—2013—10。共检索到113篇文献,其中英文文献9l篇,中文文献22篇。纳入标准：1）炎症因子的增加或减少与肺部肿瘤的关系：2）炎症因子成为治疗炎症相关性肺部肿瘤的重要靶点。根据纳入标准分析其中40篇文献。结果：白细胞介素一6（inter—leukin-6,IL-6）、移动抑制因子相关蛋白和高迁移率族蛋白Bl均属于促炎因子,在肿瘤的发生和发展中具有重要作用。IL-10和IL-13属于抑炎因子．在恶性肿瘤生长和转移的过程中可以产生截然相反的结果。结论：炎症因子与肺部肿瘤的发生、发展具有相关性,可以促进恶性细胞的增殖和存活,削弱机体的获得性免疫反应,对患者的诊断、治疗及预后有重要意义。     

肿瘤坏死因子与肿瘤的研究进展

肿瘤坏死因子与肿瘤的研究进展李光宇综述郑效审校白求恩医科大学第三临床医院（长春市１３００２１）肿瘤坏死因子（ＴｕｍｏｒＮｅｃｒｏｓｉｓＦａｃｔｏｒ，ＴＮＦ）是一种主要由单核巨噬细胞系统细胞分泌的多活性蛋白质细胞因子［１］。它不但参与机体的免疫调节、影...     

NLRP1 炎症小体与肿瘤研究进展

炎症小体是由多种蛋白质构成的复合体,是天然免疫系统的主要组成部分。炎性小体的形成能激活半胱天冬氨酸酶-1（Caspase-1）,进而引起细胞因子前体pro-IL-1β和pro-IL-18成熟和分泌并诱导细胞焦亡。NOD样受体蛋白1（nod like receptor protein 1,NLRP1）炎症小体由、接头蛋白ASC（apoptosis-associated speck-like protein containing a CARD,ASC）和效应蛋白Caspase-1构成,其激活失调与肿瘤发病机制有关,但目前在肿瘤发生和发展中的作用仍然存争议。本文就NLRP1炎症小体与肿瘤的研究进展作一综述。      

黑色素瘤缺乏因子2炎症小体在肿瘤中作用的研究进展

黑色素瘤缺乏因子2(AIM2)是非特异免疫系统中的一种感受分子,它可对细胞质中的核酸DNA进行特异性识别,启动炎症小体,从而介导炎症反应.这种炎症反应与多种疾病相关,与肿瘤的发生和发展也有一定的关联性.不同肿瘤的发病机制不同,AIM2炎症小体对不同种类肿瘤的调控机制也存在差异.本文主要从AIM2炎症小体的组成、活化机制...     

炎症小体与肿瘤转移关系的研究进展

摘 要：近年来,相当多的研究证据表明在癌症的发生和进展中涉及到炎性疾病。炎症小体以自分泌或旁分泌的方式分泌至细胞外调节细胞功能,并可对多种病原体相关分子产生应答。在炎症小体激活时,可以提高细胞防御机制。许多炎症小体通路中的关键分子如IL-1β、IL-18、Caspase-1、ASC等已被证实与多种不同类型肿瘤的发展、侵袭和转移相关。本文将主要对这些炎症小体与肿瘤转移之间的关系进行阐述。     

肿瘤免疫抑制因子研究进展

恶性肿瘤在其生长过程中能产生某些物质,造成宿主的免疫抑制,以保护肿瘤本身不受机体的攻击而继续生长。这些物质统称为免疫抑制因子。国内外对免疫抑制因子的研究,近年有所发展,现综述如下。 一、肿瘤免疫抑制因子的存在 早在1964年Graham等就发现癌症病人的体液与癌组织中存在着“耐受诱导因子”(抑制因子)。Hellstrom等1969年发现进行性Moloneg肉瘤小鼠的血清能特异地保护肿瘤细胞免受淋巴细胞的杀伤作用,并且用集落抑制试验证实了带瘤鼠血清中存在着一种“封闭因子”。Badger等发现晚期癌症病人的     

核因子-κB与炎症和肿瘤

核因子-κ B（NF-κ B）是一类近年颇受关注的细胞核转录调节因子,通过调节众多基因的转录参与多种生理、病理过程的调节.目前已至少阐明三条NF-κ B信号途径,其核心均为NFκB二聚体从抑制性分子中的释放,而且二聚体特异位点磷酸化后,才具转录调节活性.NF-κ B通过调节免疫调节因子在机体免疫中起重要作用,并通过调节炎症相关因子参与炎症反应;NF-κ B可促进细胞的增生,降低凋亡,促进血管新生和肿瘤细胞的转移能力,在肿瘤的发生、发展中起重要作用,并成为连接慢性炎症和肿瘤发生的重要分子.     

核干细胞因子与肿瘤的研究进展

核干细胞因子(nucleostemin,NS)是一个参与细胞增殖过程的正性调节蛋白.NS在多种肿瘤组织和肿瘤细胞中高表达,而在终末分化细胞中不表达,对肿瘤细胞恶性增殖和凋亡逃逸发挥着重要作用.研究发现,NS不仅通过多条途径影响细胞周期,促进细胞增殖,阻碍细胞分化,还与细胞核内的蛋白质相互作用,从不同方面促进肿瘤的形成和发展.通过对NS基因的深入研究,目前人们对肿瘤的发生机制有了更深层次的了解,这对肿瘤的诊断、治疗及预后评估将产生深远影响.本文就NS基因在肿瘤的发生、发展及致癌机制中的最新研究进展作一综述.     

炎症促发肿瘤转移的研究进展

在肿瘤微环境中,炎症细胞通过释放相关炎症因子调控相应核转录因子介导的细胞内信号传递,致使上皮细胞向间质细胞转变,最终促使肿瘤转移.由于炎症与肿瘤转移的关系密切,或许通过了解肿瘤的生物特性和相关的炎症因素,为临床制定出相应的肿瘤治疗方案,进一步提高疗效有所裨益.     

肿瘤相关性抑郁焦虑的研究进展

肿瘤患者逐年增多,对癌症患者进行综合照料管理,以期延长生存期、提高生活质量,仍属待发展领域。研究发现肿瘤患者有较高的焦虑、抑郁等精神心理异常发病率,且直接影响患者的治疗和预后。笔者从肿瘤相关性焦虑、抑郁等精神心理异常的基础研究进展与临床治疗等方面进行综述,以期采取有效措施积极干预肿瘤患者的心理问题,提高我国肿瘤患者综合治疗的疗效。     

Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms

Mutations in JAK2, MPL and CALR genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes. Overall, 30 nonsynonymous somatic mutations were detected in 12 (75%) patients with a range of 1–5 mutations per sample. Notably, one ET patient was found to have JAK2V617F and KITP551L mutations at very low allele frequency. One MPLP70L and 1 MPLM602T mutations were identified each in 1 ET and 1 PV, respectively. Other recurrent mutations were also identified including KMT2C, KMT2D, IRS2, SYNE1, PDE4DIP, SETD2, ATM, TNFAIP3 and CCND2. In addition, germline mutations were also found in some cancer-related genes. Copy number changes were rare in this cohort of TN MPNs. In conclusion, both somatic and germline mutations can be detected in TN MPN patients.     

第二代测序技术在实体瘤诊治方面的研究进展

二代测序（next-generation sequencing,NGS）也称为大规模并行测序或深度测序。这种高通量技术可以在单次运行中产生数十亿个超过几百万兆字节数据的短DNA或RNA片段。由于二代测序技术具有探索新的生物标志物并靶向识别特异性基因突变的能力,并且仅需要少量的DNA,使得通过二代测序进行分子检测广泛的应用于肿瘤的诊断和治疗。随着科学技术的进步,目前已经将二代测序平台引入个体化癌症治疗和精准医学,包括对癌症患者的精准分层、肿瘤生物学预测、治疗方案的制定、预后评估等。本文主要对近几年二代测序应用于实体肿瘤学领域的技术发展作一综述,并回顾了近几年部分相关临床研究及二代测序技术应用的重要里程碑。     

Assessing tumor heterogeneity and emergence mutations using next-generation sequencing for overcoming cancer drugs resistance

Durable anti-tumor activity of cancer-targeted drugs therapy is a major focus of current and emerging research. However, primary or acquired resistance is a big problem for the vast majority of approved targeted drugs . This, along with the high complexity of cancer development and metastasis, explains the slow progress in curing cancer . Intensive efforts are underway to understand molecular mechanisms underlying resistance essential for developing more effective agent’s combinations. Cancer genome heterogeneity for breast cancer and renal cancer , and the emergence of driver mutations in wild-type KRAS metastatic colorectal cancer , revealed by high-throughput next-generation sequencing (NGS) technologies, are some of the causes of resistance to currently used targeted drugs. Here, we discuss how the personalized tumor mutational landscape, together with future advances in systems science, network biology, systems pharmacology and interactome-based approaches for next-generation drugs and biomarkers are used to overcome resistance and improve survival and cure rates .     

Characterization of somatic mutations and pathway alterations during hepatocellular carcinoma vascular invasion using next-generation sequencing

BackgroundVascular invasion is an independent risk factors for recurrence and poor prognosis in patients with hepatocellular carcinoma (HCC). However, the molecular mechanisms of HCC vascular invasion are largely unknown. Deciphering the molecular changes associated with the vascular invasion process will aid in the identification of therapeutic targets and treatment for patients with HCC.MethodsDNA was extracted from tumor specimens and blood samples collected from 50 patients with HCC. Next-generation sequencing (NGS) was performed to detect HCC gene variants. Bioinformatics methods were used to comprehensively analyze the three sets of sequencing data grouped by vascular invasion, including differences in tumor mutation burden (TMB), mutation characteristics, and alterations in signaling pathways.ResultsBioinformatics analysis detected a total of 762 single nucleotide variants (SNVs). The TMB was not significantly different between patients with macrovascular invasion, microvascular invasion (MVI), or avascular invasion. Ten genes related to prognosis or recurrence, and one oncogene related to vascular invasion were screened. Compared with the avascular invasion cluster, the variant genes in the macrovascular and MVI clusters were mainly enriched in the thyroid hormone signaling pathway. In addition, macrovascular invasion variant genes were also enriched in the insulin signaling pathway and the Fanconi anemia pathway.ConclusionsSomatic mutations and pathway changes associated with vascular invasion in HCC were identified. The discovery of the molecular drivers of vascular invasion in HCC provides novel insights that can help guide further patient diagnosis and personalized therapy.     

二代测序技术检测鼻咽癌相关基因突变与临床病理特征关系分析

目的:以二代测序(N GS)为基础分析鼻咽癌相关基因突变及突变功能区域,探讨突变基因与临床特征之间的关系及临床应用价值.方法:收集2018年2月-2018年11月中南大学湘雅医学院附属肿瘤医院/湖南省肿瘤医院头颈放疗二科28例初治鼻咽癌患者,采用基因测序平台Illumina NextSeqCN500进行全基因测序,描述...     

二代测序在急性髓系白血病中的应用

 二代测序（NGS）目前被广泛用于急性髓系白血病（AML）的检测,由于其具有高通量、高灵敏度特性,为AML的诊断、治疗与预后判断带来了新的进展。在第54届美国血液学会（ASH）年会上关于NGS在AML中的应用有大量的报道,反映了NGS这门新技术在现代血液病诊治中的重要地位及对血液病未来发展的影响。     

Targeted next-generation sequencing identifies clinically relevant mutations in patients with chronic neutrophilic leukemia at diagnosis and blast crisis

Purpose

Chronic neutrophilic leukemia is a rare form of myeloproliferative neoplasm characterized by mature neutrophil hyperleukocytosis. The majority of patients harbor somatic mutations of CSF3R gene and are potentially amenable to targeted therapy with JAK inhibitors. The incidence and clinical significance of additional mutations requires clarification.

Materials and methods

A next-generation sequencing approach for myeloid malignancy-associated mutations was applied to diagnostic and matched blast crisis samples from four chronic neutrophilic leukemia patients.

Results

Next-generation sequencing confirmed the CSF3R T618I in all patients with identification of concurrent SRSF2, SETBP1, NRAS and CBL mutations at diagnosis. At blast crisis, clonal evolution was evidenced by an increased CSF3R T618I allele frequency and by loss or acquisition of CBL and NRAS mutations.

Conclusion

The diagnostic utility of a targeted next-generation sequencing approach was clearly demonstrated with the identification of additional mutations providing the potential for therapeutic stratification of chronic neutrophilic leukemia patients.

     

Clinical massively parallel next-generation sequencing analysis of 409 cancer-related genes for mutations and copy number variations in solid tumours

Background:

In a clinical diagnostic laboratory, we evaluated the applicability of the Ion Proton sequencer for screening 409 cancer-related genes in solid tumours.

Methods:

DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue biopsy specimens of 55 solid tumours (20 with matched normal tissue) and four cell lines and screened for mutations in 409 genes using the Ion Proton system. The mutation profiles of these samples were known based on prior testing using the Ion Torrent Personal Genome Machine (46-gene hotspot panel), Sanger sequencing, or fluorescence in situ hybridisation (FISH). Concordance with retrospective findings and additional mutations were evaluated. Assay sensitivity and reproducibility were established. Gene copy number variations (CNVs) detected were confirmed by molecular inversion probe (MIP) array.

Results:

The average Ion Proton (409-gene panel) sequencing output per run was 8 gigabases with 128 million sequencing reads. Of the 15,992 amplicons in the 409-gene panel, 90% achieved a minimum average sequencing depth of 100X. In 59 samples, the Ion Proton detected 100 of 105 expected single-nucleotide variants (SNVs) and all expected deletions (n=8), insertions (n=5), and CNVs (n=7). Five SNVs were not detected due to failed amplification of targeted regions. In 20 tumours with paired normal tissue, Ion Proton detected 37 additional somatic mutations, several in genes of high prognostic or therapeutic significance, such as MET, ALK, TP53, APC, and PTEN. MIP array analysis confirmed all CNVs detected by Ion Proton.

Conclusions:

The Ion Proton (409-gene panel) system was found to be well suited for use in a clinical molecular diagnostic laboratory. It can simultaneously screen 409 genes for a variety of sequence variants in multiple samples using a low input of FFPE DNA with high reproducibility and sensitivity.