Bench to bedside: recent advances in lung cancer pathological research with implications for diagnostic clinical practice

After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.     

Eugenics,Epigenetics, and Obesity Predisposition among Mexican Mestizos

ABSTRACT

We compare the discourses on obesity found in early- and mid-twentieth century Mexican public discourse with those of Mexican geneticists and doctors today. We argue that postgenomic shifts towards non-determinism, apparently contained in current openness to epigenetics, need to be considered alongside the persistence of racialized genetic determinisms, and alongside the potential for epigenetic environmental determinisms. By exploring the environmentalist explanations of earlier eugenic thinking about obesity, we trace continuities in the gendered and racialized framings of obesity, which risk stigmatizing indigenous ancestry and attributing blame to individual mothers.     

A bronchial-airway gene-expression classifier to improve the diagnosis of lung cancer: Clinical outcomes and cost-effectiveness analysis

Bronchoscopy is the safest procedure for lung cancer diagnosis when an invasive evaluation is required after imaging procedures. However, its sensitivity is relatively low, especially for small and peripheral lesions. We assessed benefits and costs of introducing a bronchial gene-expression classifier (BGC) to improve the performance of bronchoscopy and the overall diagnostic process for early detection of lung cancer. We used discrete-event simulation to compare clinical and economic outcomes of two different strategies with the standard practice in former and current smokers with indeterminate nodules: (i) location-based strategy—integrated the BGC to the bronchoscopy indication; (ii) simplified strategy—extended use of bronchoscopy plus BGC also on small and peripheral lesions. Outcomes modeled were rate of invasive procedures, quality-adjusted-life-years (QALYs), costs and incremental cost-effectiveness ratios. Compared to the standard practice, the location-based strategy (i) reduced absolute rate of invasive procedures by 3.3% without increasing costs at the current BGC market price. It resulted in savings when the BGC price was less than $3,000. The simplified strategy (ii) reduced absolute rate of invasive procedures by 10% and improved quality-adjusted life expectancy, producing an incremental cost-effectiveness ratio of $10,109 per QALY. In patients with indeterminate nodules, both BGC strategies reduced unnecessary invasive procedures at high risk of adverse events. Moreover, compared to the standard practice, the simplified use of BGC for central and peripheral lesions resulted in larger QALYs gains at acceptable cost. The location-based is cost-saving if the price of classifier declines.     

Age-related variations in gene expression patterns of renal cell carcinoma

Background

Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.

Conserved pan-cancer microenvironment subtypes predict response to immunotherapy

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布鲁氏菌A19疫苗株全基因组测序及比较基因组学分析

目的 探索布鲁氏杆菌A19疫苗株全基因组的结构、分子生物学的功能,并对其生物信息学进行研究。方法 采用Illumina Hiseq 4000和PacBio对A19进行全基因组测序,并与GenBank 上的8株菌进行比较基因组学解析。A19基因组3 286 167 bp, 预测3 371个基因,GC含量57.25%。通过注释COG库,对应基因有2 560个,将其归入22类COG中;根据比对KEGG库,得到2 544个基因,共参与33类代谢通路。结果 综合两个数据库结果发现,大多数A19预测基因中的基因功能主要与膜运输、氨基酸转运及碳水化合物代谢有关。结论 通过分析发现, A19和猪羊牛种布鲁氏菌之间存在一定差异,并找出牛种毒力基因。本实验通过测序A19全基因组,为布鲁菌疫苗的研究提供思路。     

冠心病血瘀证基因组学研究进展＊

目的 系统综述冠心病血瘀证基因组学研究的方法和内容。方法 计算机检索Medline、Cochrane Central Register of Controlled Trials、中国知网、万方数据库，查找冠心病血瘀证基因组学的临床研究，按照制定的纳入排除标准，由2名研究人员独立筛选文献，任何分歧通过协商一致或通过第3名研究人员来解决。结果 最终纳入34项研究，其中与冠心病血瘀证密切相关的基因组学研究类型包括基因多态性、差异基因的表达、基因的甲基化修饰，涉及的生物学功能有血管内皮损伤、血液流变学改变、炎症反应与免疫调节、血管平滑肌增殖、血脂水平等，采用的技术方法有聚合酶链式反应（Polymerase chain reaction，PCR）、飞行时间质谱技术（Time-of-flight mass spectrometry，TOF-MS）、基因芯片杂交测序（Gene Chip）等。结论 基因组学研究可阐明冠心病血瘀证的生物学基础，为冠心病血瘀证的病机演变提供更好的依据，更有助于从分子水平实现个体化治疗，从而进一步提高临床疗效。