大家好，这里是集才华与美貌与性感与骚气的大胸xie！欢迎大家来到每日22点更新的文献速递环节。今天是9月23日星期一！
今天的文献速递内容主要有：
1
醛缩酶A相互作用的治疗靶点可抑制肺癌转移并延长生存率
2
未知的半胱氨酸34号位点-血清蛋白加合物组学和DNA甲基化：N-乙酰半胱氨酸在诊断前的肺癌发生发展过程中的意义
3
可切除非小细胞肺癌临床病理相关性以及治疗方案与指南一致性
优秀的青年们，别忘了读文献哦~
阅读小提示：将DOI复制到scihub可以到查找全文~
1
Therapeutic Targeting of Aldolase A Interactions Inhibits Lung Cancer Metastasis and Prolongs Survival
醛缩酶A相互作用的治疗靶点可抑制肺癌转移并延长生存率
Cancer metabolic reprogramming promotes tumorigenesis and metastasis; however, the underlying molecular mechanisms are still being uncovered. In this study, we show that the glycolytic enzyme aldolase A (ALDOA) is a key enzyme involved in lung cancer metabolic reprogramming and metastasis. Overexpression of ALDOA increased migration and invasion of lung cancer cell lines in vitro and formation of metastatic lung cancer foci in vivo. ALDOA promoted metastasis independent of its enzymatic activity. Immunoprecipitation and proteomic analyses revealed gamma-actin binds to ALDOA; blocking this interaction using specific peptides decreased metastasis both in vitro and in vivo. Screening of clinically available drugs based on the crystal structure of ALDOA identified raltegravir, an antiretroviral agent that targets HIV integrase, as a pharmacologic inhibitor of ALDOA-gamma-actin binding that produced antimetastatic and survival benefits in a xenograft model with no significant toxicity. In summary, ALDOA promotes lung cancer metastasis by interacting with gamma-actin. Targeting this interaction provides a new therapeutic strategy to treat lung cancer metastasis. SIGNIFICANCE: This study demonstrates the role of aldolase A and its interaction with gamma-actin in the metastasis of non-small lung cancer and that blocking this interaction could be an effective cancer treatment.
JournalCancer research.
IF8.234
摘要要点
癌症的代谢重编程能够促进癌症的发生和转移，然而，潜在的分子机制尚未被阐明。在这篇文章中，作者展示了糖酵解酶醛缩酶A（ALDOA）作为一种关键酶参与了肺癌代谢重编程和转移。ALDOA的过度表达增加了肺癌细胞系在体外的迁移和侵袭，并在体内形成转移性肺癌灶。ALDOA促进肺癌的转移与其酶的活性无关。免疫沉淀反应和蛋白质组学分析显示γ-肌动蛋白与ALDOA结合在一起，使用特定的酶能够封锁这两者之间的相互作用，从而减少体内和体外的转移。根据ALDOA的晶体结构，雷特格伟（一种针对艾滋病毒整合酶的抗逆转录病毒药物）能够作为ALDOA和γ-肌动蛋白结合位点的药理学抑制剂，在无明显毒性的异种移植模型中，产生抗转移效果，提高生存收益。总的来说，ALDOA通过与γ-肌动蛋白结合来促进癌症转移。靶向作用于这个相互作用能够为治疗肺癌转移提供一种新的治疗策略。
意义：这篇文章显示了醛缩酶A与γ-肌动蛋白在非小细胞肺癌转移过程的作用，并且封锁两者之间的相互作用可以作为一种有效的癌症治疗方法。
DOI10.1158/0008-5472.CAN-18-4080
2
Agnostic Cys34-albumin adductomics and DNA methylation: implication of N-acetylcysteine in lung carcinogenesis years before diagnosis.
未知的半胱氨酸34号位点-血清蛋白加合物组学和DNA甲基化：N-乙酰半胱氨酸在诊断前的肺癌发生发展过程中的意义
Although smoking and oxidative stress are known contributors to lung carcinogenesis, their mechanisms of action remain poorly understood. To shed light into these mechanisms, we applied a novel approach using Cys34-adductomics in a lung cancer nested case-control study (n=212). Adductomics profiles were integrated with DNA-methylation >
JournalInternational journal of cancer
IF4.599
摘要要点
尽管吸烟和氧化应激已经是众所周知的肺癌促成因素，但对他们作用的机制仍缺乏了解。为了阐明吸烟和氧化应激的机制，作者在一组巢式病例对照研究（n=212）中使用半胱氨酸34号位点加合物组学的新方法。加合物组学与DNA甲基化数据整合在已建立的在同一个体中测出的与吸烟相关的CpG位点中。作者的分析显示共有42个半胱氨酸34号位点-清蛋白加合物，其中两个加合物在实验组和对照组中差异显着：N-乙酰半胱氨酸（NAC, p=4.15×10-3）和半胱氨酸-甘氨酸加合物（Cys-Gly，p=7.89×10-3）在11个吸烟相关的CpG位点上发现前者在血液中的水平其与甲基化水平有所关联。作者在前瞻性血液样本中首次发现，不论诊断时间长短，肺癌病例中NAC加合物的水平均有所下降。
总的来说，作者的结果强调了这些加合物在氧化应激反应中的潜在作用，而这些氧化应激作用促进了肺癌的被诊断之前的发生。
DOI10.1002/ijc.32680
3
Clinical-Pathologic Correlation and Guideline Concordance in Resectable Non-Small Cell Lung Cancer.
可切除非小细胞肺癌临床病理相关性以及治疗方案与指南一致性
BACKGROUND
Accurate staging of non-small cell lung cancer (NSCLC) is critical for identifying patients who will benefit from multimodality therapy.This study evaluated clinical-pathologic correlation and its effects on receipt of guideline-concordant therapy in a national cohort.
METHODS
A retrospective cohort study of patients with surgically resected NSCLC in the National Cancer Database (NCDB) between and was conducted. Primary tumor and nodal staging information was analyzed in patients who underwent upfront surgery and neoadjuvant therapy to calculate correlation between clinical and pathologic stages and estimate downstaging rate. Staging accuracy and Spearman"s rank correlation coefficients were calculated. Multivariable Cox regression was used to evaluate the association between receipt of guideline-concordant therapy and overall risk of death.
RESULTS
Among 82,999 patients, correlation between clinical and pathologic stages was strong (r = 0.69). Correlation of primary tumor staging was high (71.2%-84.5%). The positive predictive value of nodal staging was 78.2%. Neoadjuvant therapy was associated with downstaging in tumor stage (T1, 1.5%; T2, 22.6%; T3, 28%; T4, 42%) and 17.3% of positive nodes. Patients with stage I disease had high rates of guideline-concordant treatment (IA, 97.4%; and IB, 97.9%). Patients with stage IIA to IIIA disease had lower rates of guideline concordance. Receipt of guideline-concordant care was associated with a significantly lower risk of death (hazard ratio, 0.84; 95% confidence interval, 0.80-0.87).
CONCLUSION
Clinical staging modalities are reasonably accurate. However, less than one half of patients with stage IIA to IIIA NSCLC receive guideline-concordant therapy, and this deficiency is associated with inferior survival. Identifying factors contributing to these differences is crucial to improve outcomes.
JournalThe Annals of thoracic surgery.
IF3.919
摘要要点
背景:非小细胞肺癌（NSCLC）的准确分期对于识别那些能够在多模式治疗中受益的病人十分重要。本研究评估了在国家性队列研究中，患者的临床病理相关性和其在接受与指南一致的治疗后的影响。
方法:作者对国家癌症数据库中-的手术可切除的非小细胞肺癌病人进行了回顾性队列研究。对那些进行了前期手术和新辅助治疗的病人进行原发性肿瘤和结节分期信息的分析，以便计算其临床分期和病理分期的相关性和评估其肿瘤降期率。期间，进行了分期的准确性和斯皮尔曼相关系数的计算，多变量Cox回归分析被用来计算与指南一致的治疗和整体死亡风险之间的联系。
结果:在82999个病人中，临床分期和病理分期的相关性较强（r=0.69）。原发性肿瘤分期相关性高。结节分期的阳性预测值为78.2%。新辅助治疗与肿瘤的降期有关（T1: 1.5%；T2：22.6%；T3：28%；T4：42%）Ⅰ期病人使用指南一致的治疗率高（ⅠA：97.4%；ⅠB：97.9%）ⅡA期和ⅢA期的病人其治疗方式与指南的一致性较低。接受指南一致的护理与显着降低的死亡风险有关（HR：0.84；95%CI：0.80-0.87）
结论：临床分期模式是相当准确的，然而，少于半数的ⅡA-ⅢA期NSCLC病人接受了与指南一致的治疗，这个不足与低存活率有关。识别导致这些差异的因素对于提高生存率是至关重要的。
DOI10.1016/j.athoracsur..03.062
近期文献速递
.09.22 |用空间分辨和多参数单细胞分析方法分析PD-1，LAG-3和TIM-3在人类非小细胞肺癌中的表达及其意义
.09.21 | EGFR激酶结构域复制在非小细胞肺癌靶向治疗中的临床结果
文稿编译：王佳玲
图文编辑：贾婷婷
质量控制：林章宇
