NSCLC, non-small-cell lung cancer

NSCLC,非小细胞肺癌
  • 文章类型: Case Reports
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  • 文章类型: Case Reports
    一名抗核抗体阴性的非小细胞肺癌患者在免疫检查点抑制剂(ICI)给药后因呼吸困难而入院。计算机断层扫描(CT)显示复杂的放射学特征,包括胸膜下和基底占优势的网状阴影,囊性结构和支气管血管周围巩固。尽管我们在诊断为ICI相关性肺炎的情况下用大剂量类固醇治疗他,患者出现肺炎急性加重,伴有进行性纤维化和体积减少.重新评估在ICI施用前收集的血清中鉴定了抗氨酰基-tRNA合成酶抗体。此病例强调了重新评估发生ICI相关性肺炎且具有非典型放射学特征的患者先前存在的自身免疫性疾病的重要性。
    A man with non-small-cell lung cancer who was negative for anti-nuclear antibodies was admitted for dyspnea after immune checkpoint inhibitor (ICI) administration. Computed tomography (CT) showed complexed radiologic features, including subpleural and basal predominant reticular shadow with cystic structures and peribronchovascular consolidation. Although we treated him with high-dose steroid under a diagnosis of ICI-related pneumonitis, he developed acute exacerbation of pneumonitis with progressive fibrosis and volume loss. A re-evaluation identified anti-aminoacyl-tRNA synthetase antibody in the serum collected before ICI administration. This case highlights the importance of re-evaluating pre-existing autoimmune disorders in patients who develop ICI-related pneumonitis with atypical radiologic features.
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  • 文章类型: Journal Article
    RNA中的转录后修饰调节其生物学行为和功能。N1-甲基腺苷(m1A),由作者动态调节,橡皮擦和阅读器,已被发现是tRNA的可逆修饰,mRNArRNA和长链非编码RNA(lncRNA)。m1A修饰对RNA加工有影响,目标的结构和功能。越来越多的研究揭示了m1A修饰及其调节因子在肿瘤发生中的关键作用。由于m1A与癌症发展之间的正相关性,针对m1A修饰和与m1A相关的调节因子一直受到关注。在这次审查中,我们总结了目前对RNA中m1A的理解,涵盖了癌症生物学中m1A修饰的调制,以及靶向m1A修饰作为癌症诊断和治疗的潜在靶标的可能性。
    Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. N1-methyladenosine (m1A), which is dynamically regulated by writers, erasers and readers, has been found as a reversible modification in tRNA, mRNA, rRNA and long non-coding RNA (lncRNA). m1A modification has impacts on the RNA processing, structure and functions of targets. Increasing studies reveal the critical roles of m1A modification and its regulators in tumorigenesis. Due to the positive relevance between m1A and cancer development, targeting m1A modification and m1A-related regulators has been of attention. In this review, we summarized the current understanding of m1A in RNAs, covering the modulation of m1A modification in cancer biology, as well as the possibility of targeting m1A modification as a potential target for cancer diagnosis and therapy.
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  • 文章类型: Journal Article
    肺癌是全球癌症相关死亡的主要原因,最常见的肺癌亚型是腺癌。RhoQ是Rho家族GTP酶,具有与Cdc42和RhoJ的一级序列和结构相似性。RhoQ通过膜运输参与神经突生长,并且对于成熟脂肪细胞中胰岛素刺激的葡萄糖摄取至关重要。然而,RhoQ在肺腺癌(LUAD)中的作用尚不清楚.在这项研究中,将RhoQsiRNA引入A549和PC-9细胞中。采用Westernblot和transwell法检测EMT相关基因的表达水平和侵袭能力。探讨RhoQ表达与LUAD预后的关系,使用Kaplan-Meier绘图仪。我们发现抑制RhoQ表达可促进TGF-β介导的EMT和LUAD细胞系的侵袭。此外,RhoQ敲低增加Smad3磷酸化和蜗牛表达,表明RhoQ在EMT过程中参与TGF/Smad信号传导。此外,Kaplan-Meier绘图仪分析显示,低RhoQ水平与LUAD患者总体生存率低相关。总之,这些发现揭示了RhoQ在LUAD中作为TGF-β介导的EMT的负调节因子的作用。
    Lung cancer is the leading cause of cancer-related deaths worldwide, and the most common subtype of lung cancer is adenocarcinoma. RhoQ is a Rho family GTPase with primary sequence and structural similarities to Cdc42 and RhoJ. RhoQ is involved in neurite outgrowth via membrane trafficking and is essential for insulin-stimulated glucose uptake in mature adipocytes. However, the function of RhoQ in lung adenocarcinoma (LUAD) remains unclear. In this study, RhoQ siRNAs were introduced into A549 and PC-9 cells. Expression level of EMT-related genes and invasion ability were investigated using Western blot and transwell assay. To examine the relationship between RhoQ expression and prognosis of LUAD, Kaplan-Meier plotter was used. We discovered that suppressing RhoQ expression promoted TGF-β-mediated EMT and invasion in LUAD cell lines. Furthermore, RhoQ knockdown increased Smad3 phosphorylation and Snail expression, indicating that RhoQ was involved in TGF/Smad signaling during the EMT process. Moreover, Kaplan-Meier plotter analysis revealed that low RhoQ levels were associated with poor overall survival in patients with LUAD. In conclusion, these findings shed light on RhoQ\'s role as a negative regulator of TGF-β-mediated EMT in LUAD.
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  • 文章类型: Journal Article
    UNASSIGNED:肺癌(LC)患者的长期变化难以评估。我们报告了法国KBP-2020现实生活队列的结果。
    UNASSIGNED:KBP-2020是一个前瞻性队列,包括2020年在法国非学术公立医院诊断为LC的所有患者。描述了患者和肿瘤特征,并与2000年和2010年类似设计的队列进行了比较。
    未经评估:2020年,82个中心包括8,999名诊断为LC的患者。女性比例增加:34%(3114/8999),2010年和2000年为24·3%(1711/7051)和16·0%(904/5667)(p<0·0001)。2020年不吸烟者的比例更高(12.6%,1129/8983)比以前的队列(2010年为10·9%(762/7008);2000年为7·2%(402/5586),p<0·0001)。2020年,在诊断时,57·6%(4405/7648)的患者患有转移性/播散期非小细胞肺癌(NSCLC)(2010年为58·3%(3522/6046);2000年为42·6%(1879/4411),p<0·0001)。与2000年和2010年的数据相比,早期生存率略有改善。2020年,NSCLC的3个月死亡率从局部的3·0%[2·2-3·8]到局部晚期的9·6%[8·1-11·0]到转移性的29·2%[27·8-30·6],SCLC为24·8%[22·3-27·3]。
    未经评估:据我们所知,KBP队列是最大的,prospective,在全球范围内进行的涉及LC患者的真实世界队列研究.在我们的研究中发现的趋势表明,女性LC的增加,并且仍然有很大一部分被诊断为转移或扩散期的患者。
    UNASSIGNED:该研究由法国综合医院肺科医师学院在工业实验室的财政支持下推广。
    UNASSIGNED: Long-term changes in lung cancer (LC) patients are difficult to evaluate. We report results from the French KBP-2020 real-life cohort.
    UNASSIGNED: KBP-2020 was a prospective cohort that included all patients diagnosed with LC in 2020, in nonacademic public hospital in France. Patient and tumour characteristics were described and compared with similarly designed cohorts in 2000 and 2010.
    UNASSIGNED: In 2020, 82 centers included 8,999 patients diagnosed with LC. The proportion of women increased: 34·6% (3114/8999) compared to, 24·3% (1711/7051) and 16·0% (904/5667) in 2010 and 2000 (p<0·0001). The proportion of non-smokers was higher in 2020 (12·6%, 1129/8983) than in previous cohorts (10·9% (762/7008) in 2010; 7·2% (402/5586) in 2000, p<0·0001). In 2020, at diagnosis, 57·6% (4405/7648) of patients had a metastatic/disseminated stage non-small-cell lung cancer (NSCLC) (58·3% (3522/6046) in 2010; 42·6% (1879/4411) in 2000, p<0·0001). Compared with 2000 and 2010 data, early survival improved slightly. In 2020, 3-month mortality of NSCLC varied from 3·0% [2·2 - 3·8] for localized to 9·6% [8·1 - 11·0] for locally advanced to 29·2% [27·8 - 30·6] for metastatic and was 24·8% [22·3 - 27·3] for SCLC.
    UNASSIGNED: To our knowledge KBP cohorts have been the largest, prospective, real-world cohort studies involving LC patients conducted in worldwide. The trend found in our study shows an increase in LC in women and still a large proportion of patients diagnosed at metastatic or disseminated stage.
    UNASSIGNED: The study was promoted by the French College of General Hospital Pulmonologists with financial support of industrials laboratories.
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  • 文章类型: Journal Article
    UNASSIGNED:目前,调强放疗(IMRT)比三维适形放疗更常用于明确的胸部放疗。我们检查了durvalumab临床可用后同步放化疗(CCRT)和IMRT的疗效。
    UNASSIGNED:我们回顾了日本七个中心接受CCRT和IMRT治疗的III期非小细胞肺癌(NSCLC)患者的临床记录,并调查了2018年5月至2019年12月的复发和生存率。该报告的主要终点是无进展生存期(PFS)。
    未经证实:在参与研究的107名患者中,87例患者依次服用durvalumab。从CCRT开始,患者的中位随访时间为29.7个月.CCRT结束时的中位PFS为20.7个月。在87名患者中,58次经历疾病复发,其中36例(62.1%)有远处转移。多因素Cox回归分析显示,对CCRT的反应良好,辐射剂量≥62Gy,和IIIA期NSCLC与延长的PFS相关(所有P=0.04)。多因素logistic回归分析显示死亡危险因素为durvalumab治疗时间≤11.7个月,免疫相关不良事件的最高等级较低,FEV1<2805mL,和辐射剂量<62Gy(分别为P=0.01、0.01、0.03和0.04)。
    未经批准:在接受使用IMRT的CCRT的NSCLC患者中,长PFS与更好的CCRT反应相关,IIIA期NSCLC,和增加的辐射剂量。durvalumab巩固的持续时间在接受CCRT和IMRT的患者的生存中也起着重要作用。(250字)
    UNASSIGNED: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available.
    UNASSIGNED: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS).
    UNASSIGNED: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively).
    UNASSIGNED: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).
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  • 文章类型: Journal Article
    尽管对患者和临床医生来说是一个共同的挑战,在被诊断患有潜在可治愈癌症的个体中,关于心血管疾病(CVD)患病率的人群水平证据很少.
    我们调查了患有常见潜在可治愈恶性肿瘤的患者的CVD发生率,并评估了患者与疾病特征和CVD患病率之间的关联。
    该研究包括在英格兰诊断为I至III期乳腺癌的癌症登记患者,I至III期结肠癌或直肠癌,I至III期前列腺癌,I至IIIA期非小细胞肺癌,I至IV期弥漫性大B细胞淋巴瘤,2013年至2018年I至IV期霍奇金淋巴瘤。使用关联的医院记录和国家CVD数据库来识别CVD。根据肿瘤类型调查CVD的发生率,并确定患者和疾病特征与CVD患病率之间的关联。
    在634,240名患者中,102,834(16.2%)先前有CVD。男人,老年患者,生活在贫困地区的人心血管疾病发病率较高。非小细胞肺癌的患病率最高(36.1%),乳腺癌的患病率最低(7.7%)。调整后的年龄,性别,多重剥夺指数的收入域,和Charlson合并症指数,与乳腺癌患者相比,其他肿瘤类型的CVD仍然较高。
    癌症和CVD负担之间存在显着的重叠。在评估国家和国际治疗模式和癌症结局时,必须考虑CVD。
    UNASSIGNED: Although a common challenge for patients and clinicians, there is little population-level evidence on the prevalence of cardiovascular disease (CVD) in individuals diagnosed with potentially curable cancer.
    UNASSIGNED: We investigated CVD rates in patients with common potentially curable malignancies and evaluated the associations between patient and disease characteristics and CVD prevalence.
    UNASSIGNED: The study included cancer registry patients diagnosed in England with stage I to III breast cancer, stage I to III colon or rectal cancer, stage I to III prostate cancer, stage I to IIIA non-small-cell lung cancer, stage I to IV diffuse large B-cell lymphoma, and stage I to IV Hodgkin lymphoma from 2013 to 2018. Linked hospital records and national CVD databases were used to identify CVD. The rates of CVD were investigated according to tumor type, and associations between patient and disease characteristics and CVD prevalence were determined.
    UNASSIGNED: Among the 634,240 patients included, 102,834 (16.2%) had prior CVD. Men, older patients, and those living in deprived areas had higher CVD rates. Prevalence was highest for non-small-cell lung cancer (36.1%) and lowest for breast cancer (7.7%). After adjustment for age, sex, the income domain of the Index of Multiple Deprivation, and Charlson comorbidity index, CVD remained higher in other tumor types compared to breast cancer patients.
    UNASSIGNED: There is a significant overlap between cancer and CVD burden. It is essential to consider CVD when evaluating national and international treatment patterns and cancer outcomes.
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  • 文章类型: Journal Article
    The use of passively scattered proton therapy (PSPT) or intensity modulated proton therapy (IMPT) opens the potential for dose escalation or critical structure sparing in thoracic malignancies. While the latter offers greater dose conformality, dose distributions are subjected to greater uncertainties, especially due to interplay effects. Exploration in this area is warranted to determine if there is any dosimetric advantages in using IMPT for thoracic malignancies. This review aims to both compare organs-at-risk sparing and plan robustness between PSPT and IMPT and examine the mitigation strategies for the reduction of interplay effects currently available. Early evidence suggests that IMPT is dosimetrically superior to PSPT in thoracic malignancies. Randomised control trials are required before any clinical benefit of IMPT can be confirmed.
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  • 文章类型: Journal Article
    我们先前的研究表明,静脉内维生素C(IVC)治疗与调制热疗(mEHT)同时使用是安全的,并改善了非小细胞肺癌(NSCLC)患者的生活质量(QoL)。该试验的目的是进一步验证上述联合疗法在先前治疗的难治性晚期(IIIb或IV期)NSCLC患者中的疗效。共有97例患者随机接受IVC和mEHT加最佳支持治疗(BSC)(n=49,在活动臂中,同时接受1g/kg*dIVC和mEHT,每周三次,共25次治疗)或单独使用BSC(对照组中n=48)。经过24个月的中位随访,与单独使用BSC相比,联合治疗的无进展生存期(PFS)和总生存期(OS)显着延长(PFS:3个月vs1.85个月,P<0.05;OS:9.4个月vs5.6个月,P<0.05)。尽管疾病处于晚期,但活动臂的QoL显着增加。治疗后3个月疾病控制率主动臂为42.9%,对照臂为16.7%(P<0.05)。总的来说,IVC和mEHT可能具有改善晚期NSCLC患者预后的能力。
    Our previous study indicated that intravenous vitamin C (IVC) treatment concurrent with modulated electrohyperthermia (mEHT) was safe and improved the quality of life (QoL) of non-small-cell lung cancer (NSCLC) patients. The aim of this trial was to further verify the efficacy of the above combination therapy in previously treated patients with refractory advanced (stage IIIb or IV) NSCLC. A total of 97 patients were randomized to receive IVC and mEHT plus best supportive care (BSC) (n = 49 in the active arm, receiving 1 g/kg * d IVC concurrently with mEHT, three times a week for 25 treatments in total) or BSC alone (n = 48 in the control arm). After a median follow-up of 24 months, progression-free survival (PFS) and overall survival (OS) were significantly prolonged by combination therapy compared to BSC alone (PFS: 3 months vs 1.85 months, P < 0.05; OS: 9.4 months vs 5.6 months, P < 0.05). QoL was significantly increased in the active arm despite the advanced stage of disease. The 3-month disease control rate after treatment was 42.9% in the active arm and 16.7% in the control arm (P < 0.05). Overall, IVC and mEHT may have the ability to improve the prognosis of patients with advanced NSCLC.
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  • 文章类型: Journal Article
    循环微小RNA(miRNA)是用于癌症检测的有前景的生物标志物。然而,缺乏非小细胞肺癌(NSCLC)的多种族和多中心研究.我们招募了221名NSCLC患者,来自中国和美国的161个对照和56个良性结节。使用TaqMan低密度阵列进行初始miRNA筛选,然后通过RT-qPCR在中国队列中单独确认。最后,我们进行了一项来自美国队列的盲试验,以验证我们的发现.RT-qPCR证实miR-483-5p,miR-193a-3p,与对照组相比,患者的miR-25、miR-214和miR-7显著升高。这五个血清miRNA组的ROC曲线的曲线下面积(AUC)为0.976(95%CI,0.939-1.0;P<0.0001)和0.823(95%CI,0.75-0.896;P<0.0001),分别。在盲目的审判中,该小组对美国队列中95%的NSCLC病例和84%的对照进行了正确分类.最重要的是,该小组能够区分NSCLC和良性结节,在美国队列中AUC为0.979(95%CI,0.959-1.0),并允许正确预测中国和美国队列中86%和95%的I-II期肿瘤,分别。该血清miRNA组具有诊断种族不同的NSCLC患者的潜力。
    Circulating microRNAs (miRNAs) are promising biomarkers for cancer detection. However, multiethnic and multicentric studies of non-small-cell lung cancer (NSCLC) are lacking. We recruited 221 NSCLC patients, 161 controls and 56 benign nodules from both China and America. Initial miRNA screening was performed using the TaqMan Low Density Array followed by confirming individually by RT-qPCR in Chinese cohorts. Finally, we performed a blind trial from an American cohort to validate our findings. RT-qPCR confirmed that miR-483-5p, miR-193a-3p, miR-25, miR-214 and miR-7 were significantly elevated in patients compared to controls. The areas under the curve (AUCs) of the ROC curve of this five-serum miRNA panel were 0.976 (95% CI, 0.939-1.0; P < 0.0001) and 0.823 (95% CI, 0.75-0.896; P < 0.0001) for the two confirmation sets, respectively. In the blind trial, the panel correctly classified 95% NSCLC cases and 84% controls from the American cohort. Most importantly, the panel was capable of distinguishing NSCLC from benign nodules with an AUC of 0.979 (95% CI, 0.959-1.0) in the American cohort and allowed correct prediction of 86% and 95% stage I-II tumors in the Chinese and American cohorts, respectively. This serum miRNA panel holds the potential for diagnosing ethnically diverse NSCLC patients.
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