Journal of cancer epidemiology & treatment最新文献

英文中文

Journal of cancer epidemiology & treatment

Pub Date : 2019-06-26 DOI: 10.24218/JCET.2019.21

E. Reddy

Pulmonary arterial hypertension (PAH) is a chronic debilitating cardiopulmonary disease characterized by abnormal remodeling of peripheral lung vasculature resulting in progressive vasoconstriction. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible disease that is often associated with significant morbidity and poor quality of life. The prognosis of PAH and IPF is poor and currently available medications focus on relieving symptoms and slowing down progression. Hence, there is a clear necessity to develop new therapies. ETS-related genes and Friend leukemia integration–1 (FLI–1) are transcription factors involved in angiogenesis, cellular homeostasis, vascular remodeling, and the genetic regulation of inflammation, apoptosis, and fibrosis seen in PAH and IPF. Simultaneous small-interfering-RNA (siRNA) knockdown of ERG and FLI1 in human pulmonary artery endothelial cells (HPAEC) and human pulmonary microvasculature endothelial cells (HPMEC) has been associated with up-regulation of pro-inflammatory genes and interferon (IFN) pathway-related genes. Notably, the endothelium in normal lungs has also been shown to have high levels of nuclear ERG and Fli-1 compared to significantly lower levels in diseased lungs. Recently, ERG upregulation was found to promote liver homoeostasis by regulating canonical TGFβ1SMAD signaling and promoting the SMAD1 pathway while repressing SMAD3 activity. Improvement in pulmonary fibrosis through medications that suppress the TGF-β1/Smad3 pathway has also been a subject of study. In this review, we hypothesize that targeting the regulation of ERG, FLI-1 and ERG-mediation of TGF-β1/Smad3 signaling may be a promising therapeutic strategy in PAH and IPF. Keyword: Pulmonary Diseases, ETS genes, Signaling pathways, Targeted therapy, small molecules, Smad3 inhibitors, ERG/Fli-1 inducers.

肺动脉高压（PAH）是一种慢性衰弱性心肺疾病，其特征是肺外周血管系统的异常重塑导致进行性血管收缩。特发性肺纤维化（IPF）是一种慢性、进行性和不可逆的疾病，通常与严重的发病率和较差的生活质量有关。PAH和IPF的预后较差，目前可用的药物侧重于缓解症状和减缓进展。因此，开发新疗法显然是必要的。ETS相关基因和Friend白血病整合-1（FLI-1）是参与血管生成、细胞稳态、血管重塑以及PAH和IPF中炎症、细胞凋亡和纤维化的遗传调控的转录因子。人肺动脉内皮细胞（HPAEC）和人肺微血管内皮细胞（HPMEC）中ERG和FLI1的同时小干扰RNA（siRNA）敲低与促炎基因和干扰素（IFN）通路相关基因的上调有关。值得注意的是，与病变肺中明显较低的水平相比，正常肺中的内皮细胞也显示出高水平的核ERG和Fli-1。最近，ERG上调被发现通过调节经典的TGFβ1SMAD信号传导和促进SMAD1途径同时抑制SMAD3活性来促进肝脏稳态。通过抑制TGF-β1/Smad3途径的药物改善肺纤维化也是一个研究主题。在这篇综述中，我们假设靶向ERG、FLI-1和ERG介导的TGF-β1/Smad3信号传导可能是PAH和IPF的一种有前途的治疗策略。关键词：肺部疾病，ETS基因，信号通路，靶向治疗，小分子，Smad3抑制剂，ERG/Fli-1诱导剂。

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引用次数: 0

Anal Squamous Cell Carcinoma in African Americans with and without HIV: A Comparative Study 非裔美国人携带和不携带HIV的肛门鳞状细胞癌的比较研究

Journal of cancer epidemiology & treatment

Pub Date : 2015-07-03 DOI: 10.24218/JCET.2015.04

C. Lokko, J. Turner, Wonsuk Yoo, D. Wood, Kyra P Clark, E. Childs, V. Rao, E. Reddy, C. Clark

Background The incidence of anal carcinoma has increased over the last few decades especially in African Americans (AA) despite the use of highly active anti-retroviral therapy (HAART). Here, we retrospectively review oncologic outcomes of AA patients with anal squamous cell carcinoma (SCC) with and without HIV to further examine the cause of this trend. Materials and Methods All adult AA patients diagnosed with anal SCC from 2000 to 2007 who met inclusion were examined. All patients were staged according to the American Joint Committee on Carcinoma (AJCC) sixth edition staging classification. Patients were divided into two cohorts: HIV (−) and HIV (+). Demographics, comorbidities, and oncologic outcomes were analyzed. Results Twenty-two AA patients with anal SCC were analyzed. Fifteen (68.%) were HIV (+) and seven (32%) were negative. Seventy-four percent of HIV (+) patients were on HAART therapy at the time of diagnosis. The HIV (+) cohort was significantly younger, mostly male, and had more comorbidities compared to the negative cohort. There was no difference in tumor, nodal or metastasis (TNM) stage for both cohorts. HIV (+) patients were more likely to receive non-operative therapy. The 5-year survival rate for HIV negative and positive patients was 57% and 58%, respectively. AJCC stage was the only factor predictive of survival after performing Cox hazard proportional regression analysis, HR: 1.96 (95% CI, 0.987 to 3.881). Conclusions In the HAART era, HIV (+) AA patients are at high risk of developing anal SCC. However, the prognosis of HIV (+) AA with anal SSC is similar to that of their HIV (−) counterparts. Carcinoma stage is the only factor predictive of survival.

在过去的几十年里，尽管使用了高效抗逆转录病毒治疗(HAART)，但肛门癌的发病率仍在增加，尤其是在非洲裔美国人(AA)中。在这里，我们回顾性地回顾了AA患者合并肛门鳞状细胞癌(SCC)伴HIV和不伴HIV的肿瘤预后，以进一步研究这种趋势的原因。材料与方法对2000 ~ 2007年诊断为肛门鳞状细胞癌的成人AA患者进行检查。所有患者均根据美国癌症联合委员会(AJCC)第六版分期分类进行分期。患者分为两组:HIV(−)和HIV(+)。分析了人口统计学、合并症和肿瘤学结果。结果对22例AA合并肛门鳞状细胞癌患者进行分析。阳性15例(68%)，阴性7例(32%)。在诊断时，74%的HIV(+)患者正在接受HAART治疗。HIV(+)组明显更年轻，主要是男性，与阴性组相比有更多的合并症。两组患者的肿瘤、淋巴结或转移(TNM)分期无差异。HIV阳性患者更有可能接受非手术治疗。HIV阴性和阳性患者的5年生存率分别为57%和58%。Cox风险比例回归分析后，AJCC分期是预测患者生存的唯一因素，风险比为1.96 (95% CI, 0.987 ~ 3.881)。结论在HAART时代，HIV (+) AA患者是发生肛门SCC的高危人群。然而，伴有肛门SSC的HIV (+) AA的预后与HIV(−)AA的预后相似。肿瘤分期是预测生存的唯一因素。

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引用次数: 3

Potential Risks in the Paradigm of Basic to Translational Research: A Critical Evaluation of qPCR Telomere Size Techniques. 从基础到转化研究范式的潜在风险:qPCR端粒大小技术的关键评估。

Journal of cancer epidemiology & treatment

Pub Date : 2015-01-01 Epub Date: 2015-08-12 DOI: 10.24218/jcet.2015.08

Arthur J Lustig

Real time qPCR has become the method of choice for rapid large-scale telomere length measurements. Large samples sizes are critical for clinical trials, and epidemiological studies. QPCR has become such routine procedure that it is often used with little critical analysis. With proper controls, the mean telomere size can be derived from the data and even the size can be estimated. But there is a need for more consistent and reliable controls that will provide closer to the actual mean size can be obtained with uniform consensus controls. Although originating at the level of basic telomere research, many researchers less familiar with telomeres often misunderstand the source and significance of the qPCR metric. These include researchers and clinicians who are interested in having a rapid tool to produce exciting results in disease prognostics and diagnostics than in the multiple characteristics of telomeres that form the basis of the measurement. But other characteristics of the non-bimodal and heterogeneous telomeres as well as the complexities of telomere dynamics are not easily related to qPCR mean telomere values. The qPCR metric does not reveal the heterogeneity and dynamics of telomeres. This is a critical issue since mutations in multiple genes including telomerase can cause telomere dysfunction and a loss of repeats. The smallest cellular telomere has been shown to arrest growth of the cell carrying the dysfunction telomere. A goal for the future is a simple method that takes into account the heterogeneity by measuring the highest and lowest values as part of the scheme to compare. In the absence of this technique, Southern blots need to be performed in a subset of qPCR samples for both mean telomere size and the upper and lower extremes of the distribution. Most importantly, there is a need for greater transparency in discussing the limitations of the qPCR data. Given the potentially exciting qPCR telomere size results emerging from clinical studies that relate qPCR mean telomere size estimates to disease states, the current ambiguities have become urgent issues to validate the findings and to set the right course for future clinical investigations.

实时qPCR已成为快速大规模端粒长度测量的首选方法。大样本量对临床试验和流行病学研究至关重要。QPCR已经成为如此常规的程序，以至于它经常被用于很少的批判性分析。通过适当的控制，可以从数据中得出平均端粒大小，甚至可以估计端粒大小。但是，需要更一致和可靠的控制，以提供更接近实际的平均大小，可以通过统一的共识控制。虽然起源于基础端粒研究水平，但许多不太熟悉端粒的研究人员经常误解qPCR的来源和意义。其中包括研究人员和临床医生，他们感兴趣的是拥有一种快速工具，在疾病预后和诊断方面产生令人兴奋的结果，而不是端粒的多种特征，这些特征构成了测量的基础。但非双峰和异构端粒的其他特征以及端粒动力学的复杂性，不容易与qPCR平均端粒值相关联。qPCR指标并没有揭示端粒的异质性和动态。这是一个关键问题，因为包括端粒酶在内的多个基因突变会导致端粒功能障碍和重复序列的丢失。最小的细胞端粒已被证明可以阻止携带功能障碍端粒的细胞的生长。未来的目标是一种简单的方法，通过测量最高和最低的值来考虑异质性，作为比较方案的一部分。在没有这种技术的情况下，需要在qPCR样品的一个子集中进行Southern印迹，以获得平均端粒大小和分布的上下极值。最重要的是，在讨论qPCR数据的局限性时需要更大的透明度。考虑到qPCR端粒大小从临床研究中出现的潜在令人兴奋的结果，将qPCR平均端粒大小估计与疾病状态联系起来，目前的模糊性已成为验证研究结果并为未来临床研究设定正确路线的紧迫问题。

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引用次数: 5

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