Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature

Introduction

Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making.

Psychological impact of comprehensive tumor genomic profiling results for advanced cancer patients

ObjectiveComprehensive tumor genomic profiling (CTGP) is increasingly used to personalize treatments, providing hope, but potentially disappointment, for patients. We explored psychological outcomes in patients with advanced, incurable cancer, after receiving CTGP results.MethodsParticipants with advanced, incurable cancer (n = 560, mean age 56, 43% university educated) in this longitudinal substudy of the Molecular Screening and Therapeutics Program (MoST), completed questionnaires before and after receiving CGP results. MoST participants, recruited from Australian oncology clinics, undergo CTGP, and if there are actionable findings, are offered treatment in a related therapeutic trial if available.ResultsPatients who received actionable results, (n = 356, 64%) had lower gene-related distress (MICRA) (p < 0.001) and Impact of Events scores (p = 0.039) than patients with non-actionable results. Those with actionable results offered ensured access to tailored treatment (n = 151) reported lower anxiety (p = 0.002) and depressive symptoms (p = 0.01) and greater hope (p = 0.002) than those not offered. Positive attitudes towards uncertainty and higher self-efficacy for coping with results were associated with lower psychological distress and uncertainty, and higher hope and satisfaction with the decision to have CTGP (ps=0.001–0.047). Those with higher knowledge reported greater anxiety (p = 0.034).ConclusionReceiving a non-actionable CTGP result, or an actionable result without ensured access to treatment, may cause increased distress in advanced cancer patients. Coping style was also associated with distress.Practice implicationsPre-testing assessment and counseling addressing attitudes toward uncertainty and self-efficacy, and post-CTGP result support for patients receiving a non-actionable result or who receive an actionable results without ensured access to treatment, may benefit patients.     

Application of physiological genomics to the microcirculation

Physiological genomics represents a new challenge in the biological sciences-the quest to define the functions of thousands of genes that will emerge from the sequencing of the human genome and the genomes of other model organisms. Because the attention of the scientific community has focused on this task, new tools that will allow high-efficiency identification of gene function are being developed at remarkable speed. Physiological genomic approaches to understanding integrated systems function are now becoming widely used in many areas of biological research. The availability of genomic information across species has now revealed a striking degree of conservation of both gene order and function, allowing researchers to easily move from model organisms to man in the hunt for gene function. Physiological genomics approaches in the cardiovascular system have focused on disease-based models and the behavior of large vessels. In the microcirculation, genomic studies have largely been confined to the use of single gene knockouts or to the study of angiogenesis. This review summarizes the strategies for physiological genomics that are appropriate to the study of the microcirculation and discusses several key discoveries that have been made by using these approaches.     

Applying mental model methods to characterize understanding of gene-environment influences: the case of podoconiosis in Ethiopia

The rapid pace of genomic discovery has raised public expectation and concerns about the utility of new discoveries and their potential to exacerbate health disparities. Improving literacy concerning gene and environmental (GxE) contributors to disease is needed to avoid commonly observed deterministic misconceptions about genomics. Mental models approaches that incorporate community engagement processes could be used to inform GxE literacy-building interventions. We used a mental models approach to describe and systematically compare expert and lay understanding of GxE interactions, using the example of podoconiosis, a non-infectious lymphedema endemic in highland Ethiopia. Methods included: (1) specifying elicitation questions for a literature review, (2) eliciting an expert model, (3) eliciting a lay model, and (4) comparing the two models. We used a coding scheme to identify lay participants’ knowledge gaps, misunderstandings, and extra knowledge relative to the expert standard. Results indicated that lay participants’ viewed poverty as an important susceptibility factor and considered heredity and contagion to have a joint causal influence. Experts did not endorse either of these viewpoints. Conventional expert-based interventions aimed to correct misconceptions about behaviors important for prevention may be stymied by lay views that social environmental factors have more important influences on health outcomes. GxE literacy interventions that consider multiple levels of influence including social determinants of health and personal resilience to augment health education strategies are needed in diverse settings. Novel communication approaches will be needed to help target audiences disentangle long-held conceptions of heredity and contagion.     

代谢组学在结直肠肿瘤中的应用进展

在后基因组时代,代谢组学是继基因组学、转录组学、蛋白质组学之后迅速崛起的一门新兴学科,是对生物体的代谢组进行系统测量分析,从而揭示机体生命活动代谢本质的科学。其在区分结直肠良恶性肿瘤和监测结直肠肿瘤的手术、化疗效果等方面具有独特的优势和临床应用价值。本文就代谢组学的概况、研究方法及其在结直肠肿瘤诊治中的应用作一综述。     

Functional Genomics Approaches to Studies of the Cytochrome P450 Superfamily

Functional genomics approaches are widely implemented in current research and have found application in many areas of biology. This review will present research fields, novel findings and new tools developed in the cytochrome P450 field using the functional genomics techniques. The most widely used method is microarray technology, which has already greatly contributed to the understanding of the cytochromes P450 function and expression. Several focused CYP microarrays have been developed for genotyping, toxicogenomics and studies of CYP function of many different organisms. Our contribution to the CYP field by development of Steroltalk microarrays to study the cross-talk of cholesterol homeostasis and drug metabolism is also presented.     

基因组学与中医药研究

随着人类基因组计划的完成及后基因组时代的到来,功能基因组学已成为新的研究重点。基因组学研究的方法学内容与中医学许多方面有相似之处,决定了两者相互渗透的可能性。同时,基因组学的发展为中医药实现现代化提供了良好的契机。目前,基因组学与中医药研究主要集中于中医证候、中药、针灸等领域,并初步取得了一些进展,但存在的问题也值得众多中医药工作者进一步思考与探讨。     

非小细胞肺癌的分子起源和表达谱

在肿瘤所导致的死亡中,非小细胞肺癌是最常见的原因之一。该病难以早期发现且预后不佳。随着基因组学、表观遗传学和蛋白质组学的研究进展,预测肺癌发生风险、判断预后、选择个体化的最佳预防和治疗模式成为可能。本文对非小细胞肺癌发生、发展和预后的分子研究进展予以综述。     

A vitronectin M381T polymorphism increases risk of hemangioblastoma in patients with VHL gene defect

Hemangioblastomas, highly vascular tumors, occur sporadically or associated with von Hippel–Lindau (VHL) disease. Diverse mutations in the VHL gene inactivate the VHL protein and constitute the molecular etiology of the disease. Changes in VHL gene were analyzed in patients with multiplex ligation-dependent probe amplification and single-strand conformation polymorphism analyses. We report here that other angiogenesis-related changes in vitronectin were identified with 2D electrophoresis of plasma samples and restriction fragment length polymorphisms. Our findings revealed that most patients (80.0%) with a familial VHL deletion carried the threonine (T) allele at vitronectin codon 381. Adults simultaneously carrying a VHL defect and the T allele were 5.0-fold more likely to be affected by VHL disease than were methionine/methionine (M/M) homozygotes carrying a VHL defect. Patients with sporadic hemangioblastoma, C-terminally truncated VHL protein or a large deletion in the VHL gene, and the T allele were 18.0-fold more likely to develop recurrent disease. Taken together, individuals with mutated VHL are more likely to be affected by familial or recurrent sporadic hemangioblastoma when carrying the M/T or T/T genotype at codon 381 of vitronectin. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

新一代DNA测序技术

近年来新型DNA测序平台454、Solexa、SOLiD、Polonator和HeliSeope等得到迅速推广,使测序成本下降了2-3个数量级.原先只能由大型测序中心完成的基因组项目,现在已经可以在个人实验室中实现.这些新技术大大加速了生物医学的研究步伐,因为全面分析基因组、转录物组和代谢组已不再是高不可攀,而将成为广泛运用的常规分析.本文介绍DNA测序新技术的原理、特点、现状和应用前景.