A practical guide to HER2 testing

Nurses are becoming increasingly involved in providing information about the full range of medical care to patients. With the identification of increasing numbers of prognostic factors in cancer, this role is extending to include testing for these factors. HER2 status has prognostic and predictive value in breast cancer and the receptor is a target for specific therapies. To identify patients who might benefit from more aggressive treatment regimens or new therapeutic options, it is vital that HER2 abnormalities are accurately measured. A variety of techniques have been developed to measure HER2 overexpression or amplification, including fluorescence in situ hybridization, immunohistochemistry, polymerase chain reaction and enzyme-linked immunosorbent assay. To date, no one test has been accepted as standard and pathology laboratories are using different tests. This has implications for the interpretation of results, which in turn has implications for the widespread use of HER2 testing. This article describes the various tests available for the measurement of HER2, identifies the features of the ideal HER2 test and which test currently best fits these criteria, and considers whether HER2 status should be a routine part of the clinical evaluation of breast cancer patients. Important information that nurses should consider when providing information on HER2 testing to patients is highlighted.     

DNA methylation analysis: a review of current methodologies

The relationship between levels of DNA methylation and gene activity has been known for some time. Many of the early procedures developed gave only somewhat limited information about methylation patterns, for example, the total level of 5-methyl cytosine in the genome or the frequency of methylation of cytosines within certain restriction sites. However, in the last few years, there has been an explosion of interest in DNA methylation, and with it, many new and powerful techniques have been developed to facilitate its study. In this paper, the key techniques currently available are reviewed and the advantages, disadvantages, and potential artifacts of each are discussed.     

Measurement of clinical performance of nurses: a literature review

Despite a 40-year history of researching and developing an instrument for measurement of clinical competence in nursing, there are none that are universally accepted for this purpose. This article presents a critical review of the research, which has been carried out to explore the measurement of nurses' clinical performance. To search the literature in a systematic manner, the criteria stipulated by the Cochrane Research Database were applied. The review showed that assessment tools have been developed using a variety of different methods and several instruments were found to have been developed but nothing that is universally accepted. However, the authors found that the pathway for instrument generation suggested by Smith and Kendall (1963) offers a robust approach to the generation of such a tool regardless of the practice setting. Other methods identified in this literature review also offer interested researchers an opportunity to explore the current role of the nurse, as well as the possibility of developing tools for assessing the performance of students at various stages in their education and nurses at various times after qualification.     

Nurse manpower demand: a review of United Kingdom methodologies

Forecasting the demand for nurses is a complex and difficult problem However, in a climate of economic cutbacks and disadvantageous demographic trends, it is essential that adequate methods are developed to predict both the supply and demand for nurse manpower To this end a number of methods have been constructed, particularly in the last decade In this paper we survey the work that has been done to provide an effective way of forecasting nurse manpower demand The two most common approaches are from the 'top-down' or 'bottom-up' However, an evolutionary method which allows for modification and detailed refinement is more likely to provide a means of taking into account the complexities of the system Finally, we focus on the nursing hours per patient (NHPP) ratio as a possible tool for demand forecasting This index is easily calculated and is readily adaptable to the bottom-up approach     

Drug-targeting methodologies with applications: A review

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system.     

Representative 2D-material-based nanocomposites and their emerging applications: a review

Composites (or complex materials) are formed from two or many constituent materials with novel physical or chemical characteristics when integrated. The individual components can be combined to create a unique composite material through mechanical transfer, physical stacking, exfoliation, derivative chemical mixtures, mixtures of solid solutions, or complex synthesis processes. The development of new composites based on emerging 2D nanomaterials has allowed for outstanding achievements with novel applications that were previously unknown. These new composite materials show massive potential in emerging applications due to their exceptional properties, such as being strong, light, cheap, and highly photodegradable, and their ability to be used for water splitting and energy storage compared to traditional materials. The blend of existing polymers and 2D materials with their nanocomposites has proven to be immediate solutions to energy and food scarcity in the world. Although much literature has been reported in the said context, we tried to provide an understanding about the relationship of their mechanisms and scope for future application in a comprehensive way. In this review, we briefly summarize the basic characteristics, novel physical and chemical behaviors, and new applications in the industry of the emerging 2D-material-based composites.

Composites (or complex materials) are formed from two or many constituent materials with novel physical or chemical characteristics when integrated.     

Polyclonal antibodies against gp185HER2 peptides: their putative role in the identification of a particular HER2 status in patients with breast cancer

The HER2 oncogene and its relative oncoprotein, gp185HER2, a transmembrane glycoprotein belonging to the epidermal growth factor receptor family, are overexpressed in a wide range of solid tumors including breast and ovarian cancer. In patients with breast cancer, both humoral and cell-mediated HER2 immune responses have been found as well as in some patients with gp185HER2 nonoverexpressing tumors. To establish whether peptide sequences identified as HLA-A2-restricted T-cell epitopes are expressed in breast tumor cell lines and tissues, we produced and characterized by different methodologic approaches polyclonal antibodies raised against four gp185HER2 peptides. Two of the antibodies recognized peptides eluted from the HLA-A2 groove of the mDAmB231 breast cancer cell line expressing a basal level of gp185HER2. Paraffin-embedded primary and metastatic breast tumors were specifically immunostained by all four reagents, thereby showing an overlapping reactivity. When this immunoreactivity was compared with that obtained using two different monoclonal antibodies, in 105 breast primary tumors and 36 corresponding lymph node metastases, we identified a subset of tumors that were negative with anti-gp185HER2 monoclonal antibodies and positive with the four antipeptide antibodies. Our novel observations provide in vivo evidence of the complexity involved in evaluating HER2 expression, and open a new path for understanding the biologic significance of HER2 status in breast tumors.     

A world apart: Inaccuracies of laboratory methodologies in antidoping testing

Antidoping testing is currently exclusively based on haematochemical analysis performed in specialized laboratories accredited by WADA (World Anti-Doping Agency). Many of the analytical methods used for the determination of the parameters considered, such as haematological parameters (haemoglobin, haematocrit and reticulocytes), proteins (soluble transferrin receptor and hepcidin) and hormones (erythropoietin and growth hormone) are often affected by lack of clear standardization and harmonization. The observed incongruity of the data deriving from different laboratories often results in the risk of false positive results in athletes.This review wants to provide additional proofs in support of the need to improve the antidoping methodology involving different research and clinical institutions and skills.     

Suboptimal performance of rotavirus testing in a vaccinated community population should prompt laboratories to review their rotavirus testing algorithms in response to changes in disease prevalence

Rotavirus vaccine has reduced disease prevalence in many countries. Consequently, we aimed to assess the reliability of a rotavirus immunoassay in the community population of Auckland and Northland, New Zealand. Between 22 October 2015 and 31 December 2016, 2873 fecal samples were tested by enzyme immunoassay (EIA, Rotascreen II, Microgen, UK) from 2748 patients (median age 8?years, range 0–101?years). Eighty-nine (3.1%) samples were reactive; 86 samples were tested by a second method. Rotavirus was confirmed in 49/86 (57%). Positive rotavirus EIAs were more likely to be confirmed in samples from cases ≥1?year of age (positive predictive value [PPV] 61%, 95% confidence interval [CI] 50–72%, P?=?0.049) and in spring/summer (PPV 67%, 95% CI 55–78%, P?=?0.003). Reactive rotavirus tests required confirmatory testing regardless of demographic, vaccine, or seasonal factors; a review of rotavirus testing algorithms may be necessary in other vaccinated community populations.     

MET和HER2在胃癌中的表达及临床意义

目的分析胃癌人群中癌基因MET、人表皮生长因子受体2(HER-2)的蛋白表达及其与临床病理学特征的关系,为探索其对胃癌根治术患者复发及生存的预测价值。方法收集2007年2月20日至2013年2月20日来接受手术切除的胃或胃食管交界处腺癌患者标本共180例。采用En Vi Sion免疫组化法和FISH法对每个标本中的MET和HER2进行其相关的基因阳性表达水平进行检测,并对二者与患者的相关个人信息、病变部位、肿瘤的分化程度、有无转移等相关信息之间的线性相关关系进行研究。观察免疫组化评分与荧光原位杂交检测HER2的高表达与基因扩增之间的重叠率。统计患者两年内病死率。结果通过对180例胃癌患者进行免疫组化以及FISH方法检测HER2发现,HER2和MET的阳性表达率是40.0%和31.1%,基因扩增率是36.7%和34.4%,HER2和MET的高表达与基因扩增之间的重叠率是73.6%和78.6%,各个免疫组化间的重叠率比较差异有显著性(P0.01)。MET表达与患者的个人信息、病变大小、病变部位以及是否出现淋巴道转移无关(P0.05),而与分化程度、临床分期以及是否出现门脉侵犯有关(P0.05);HER2表达与患者的个人信息、是否出现门脉侵犯、病变部位、是否出现淋巴道转移以及临床分期无关(P0.05),而与分化程度与病变大小有关(P0.05)。经过为期2年的随访工作发现,死亡率为33.3%(60/180),其中54例患者在检测过程中呈MET和HER2的双向高度表达。结论 MET和HER2的共同高度表达与胃癌患者病死率之间有相关性,HER2与肿瘤的分化程度和病变大小有关,MET与肿瘤分化程度和门脉侵犯有关,为今后临床上对胃癌患者癌基因的检测结果分析提供了重要的生物学资料。     

In situ hybridisation: a review of methodologies and applications in the biomedical sciences.

In situ hybridisation methodology is reviewed with particular emphasis on the latest modifications of technique. Methodology is evaluated, with suggestions on how to maximise its successful application. Emphasis is placed upon non-radioactive techniques which can be used by morphologically orientated laboratories, and details of the use of digoxigenin-labelled oligonucleotide probes are given special mention. Recent applications in morphology, and neurobiology, virology, pathology and cytogenetics are detailed. Developments where significant advances have been made in the biomedical sciences are highlighted.     

Improving the validity of clinical exercise testing: the relationship between practice and performance

Many studies involving exercise testing fail to address the issue of practice. Those that do vary considerably with respect to the parameters of practice used. We evaluated the effect of two standardized practices on a horizontal submaximal exercise test performed on a treadmill. Healthy men (n = 20) with no previous treadmill exposure were alternately assigned to the experimental (practice) or control (no practice) group. Heart rate (HR), systolic blood pressure (SBP), rate pressure product (RPP), step cadence (CAD) and perceived exertion (PE) were recorded at the end of each work load of the practices and/or tests. We observed no significant differences in these variables over the common work loads for the first practice session in the experimental group and the exercise test in the control group (p greater than 0.05). The two groups were homogeneous with respect to fitness and magnitude of arousal on initial exposure to the treadmill. During the submaximal test, HR, SBP, RPP, CAD, and PE were systematically lower for the experimental group than for the control group. The SBP and RPP were significantly lower in the experimental group (p less than 0.01). The CAD tended toward statistical significance (p less than 0.07), whereas HR and PE were not significantly different for the two groups (p greater than 0.05). When the four common work loads were compared over the two practices and the exercise test for the experimental group, SBP and CAD were significantly higher for practice 1 than for practice 2 and the test (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)