Microtubules and cadherins : a neglected partnership

Classical cadherins are fundamental determinants of tissue organization both in health and disease. It has long been recognized that cadherins function in close cooperation with the cytoskeleton, particularly with actin. Less appreciated is the capacity for cadherins to also interact functionally and biochemically with microtubules and their associated proteins. In this review, we aim to highlight the potential for cooperativity between cadherins and microtubules. Cadherins can regulate the organization and dynamics of microtubules through mechanisms such as anchorage of minus ends and cortical capture of plus ends. Such cadherin-induced reorganization of microtubules may then affect cadherin biology by diverse processes that include directed vesicular traffic by microtubule-based motors and regulation of cortical signaling and organization. Ultimately, we hope this will stimulate fresh interest and research to understand a neglected partnership.

Circulating tumour cells in metastatic head and neck cancers

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with 650,000 new cases p/a worldwide. HNSCC causes high morbidity with a 5-year survival rate of less than 60%, which has not improved due to the lack of early detection (Bozec et al. Eur Arch Otorhinolaryngol. 2013;270: 2745–9). Metastatic disease remains one of the leading causes of death in HNSCC patients. This review article provides a comprehensive overview of literature over the past 5 years on the detection of circulating tumour cells (CTCs) in HNSCC; CTC biology and future perspectives. CTCs are a hallmark of invasive cancer cells and key to metastasis. CTCs can be used as surrogate markers of overall survival and progression-free survival. CTCs are currently used as prognostic factors for breast, prostate and colorectal cancers using the CellSearch® system. CTCs have been detected in HNSCC, however, these numbers depend on the technique applied, time of blood collection and the clinical stage of the patient. The impact of CTCs in HNSCC is not well understood, and thus, not in routine clinical practice. Validated detection technologies that are able to capture CTCs undergoing epithelial–mesenchymal transition are needed. This will aid in the capture of heterogeneous CTCs, which can be compiled as new targets for the current food and drug administration-cleared CellSearch® system. Recent studies on CTCs in HNSCC with the CellSearch® have shown variable data. Therefore, there is an immediate need for large clinical trials encompassing a suite of biomarkers capturing CTCs in HNSCC, before CTCs can be used as prognostic markers in HNSCC patient management.

Label-free isolation of a prostate cancer cell among blood cells and the single-cell measurement of drug accumulation using an integrated microfluidic chip

Circulating tumor cells (CTCs) are found in the blood of patients with cancer. Although these cells are rare, they can provide useful information for chemotherapy. However, isolation of these rare cells from blood is technically challenging because they are small in numbers. An integrated microfluidic chip, dubbed as CTC chip, was designed and fabricated for conducting tumor cell isolation. As CTCs usually show multidrug resistance (MDR), the effect of MDR inhibitors on chemotherapeutic drug accumulation in the isolated single tumor cell is measured. As a model of CTC isolation, human prostate tumor cells were mixed with mouse blood cells and the labelfree isolation of the tumor cells was conducted based on cell size difference. The major advantages of the CTC chip are the ability for fast cell isolation, followed by multiple rounds of single-cell measurements, suggesting a potential assay for detecting the drug responses based on the liquid biopsy of cancer patients.

Heterogeneity of miR-10b expression in circulating tumor cells

Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as € liquid biopsyto aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch ® CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients.

Circulating tumor cell detection in high-risk non-metastatic prostate cancer

Purpose The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method. Method Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method. Results The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age. Conclusion This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.

Professional development for the integration of biotechnology education

Views on the nature and relevance of science education have changed significantly over recent decades. This has serious implications for the way in which science is taught in secondary schools, particularly with respect to teaching emerging topics such as biotechnology, which have a socio-scientific dimension and also require novel laboratory skills. It is apparent in current literature that there is a lack of adequate teacher professional development opportunities in biotechnology education and that a significant need exists for researchers to develop a carefully crafted and well supported professional development design which will positively impact on the way in which teachers engage with contemporary science. This study used a retrospective case study methodology to document the recent evolution of modern biotechnology education as part of the changing nature of science education; examine the adoption and implementation processes for biotechnology education by three secondary schools; and to propose an evidence based biotechnology professional development model for science educators. Data were gathered from documents, one-on-one interviews and focus group discussions. Analysis of these data has led to the proposal of a biotechnology professional development model which considers all of the key components of science professional development that are outlined in the literature, as well as the additional components which were articulated by the educators studied. This research is timely and pertinent to the needs of contemporary science education because of its recognition of the need for a professional development model in biotechnology education that recognizes and addresses the content knowledge, practical skills, pedagogical knowledge and curriculum management components.

The criminalisation of medical mistakes in Canada : a review

The issue of health professionals facing criminal charges of manslaughter or criminal negligence causing death or grievous bodily harm as a result of alleged negligence in their professional practice was thrown into stark relief by the recent acquittal of four physicians accused of mismanaging Canada’s blood system in the early 1980s. Stories like these, as well as international reports detailing an increase in the numbers of physicians being charged with (and in some cases convicted of) serious criminal offences as the result of alleged negligence in their professional practice, have resulted in some anxiety about the apparent increase in the incidence of such charges and their appropriateness in the healthcare context. Whilst research has focused on the incidence, nature and appropriateness of criminal charges against health professionals, particularly physicians, for alleged negligence in their professional practice in the United Kingdom, the United States, Japan, and New Zealand, the Canadian context has yet to be examined. This article examines the Canadian context and how the criminal law is used to regulate the negligent acts or omissions of a health care professional in the course of their professional practice. It also assesses the appropriateness of such use. It is important at this point to state that the analysis in this article does not focus on those, fortunately few, cases where a health professional has intentionally killed his or her patients but rather when patients’ deaths or grievous injuries were allegedly as a result of that health professional’s negligent acts or omissions when providing health services to that patient.

Paramedic knowledge of infectious disease aetiology and transmission in an Australian Emergency Medical System

Introduction: Paramedics and other emergency health workers are exposed to infectious disease particularly when undertaking exposure-prone procedures as a component of their everyday practice. This study examined paramedic knowledge of infectious disease aetiology and transmission in the pre-hospital care environment.--------- Methods: A mail survey of paramedics from an Australian ambulance service (n=2274) was conducted.--------- Results: With a response rate of 55.3% (1258/2274), the study demonstrated that paramedic knowledge of infectious disease aetiology and modes of transmission was poor. Of the 25 infectious diseases included in the survey, only three aetiological agents were correctly identified by at least 80% of respondents. The most accurate responses for aetiology of individual infectious diseases were for HIV/AIDS (91.4%), influenza (87.4%), and hepatitis B (85.7%). Poorest results were observed for pertussis, infectious mononucleosis, leprosy, dengue fever, Japanese B encephalitis and vancomycin resistant enterococcus (VRE), all with less than half the sample providing a correct response. Modes of transmission of significant infectious diseases were also assessed. Most accurate responses were found for HIV/AIDS (85.8%), salmonella (81.9%) and influenza (80.1%). Poorest results were observed for infectious mononucleosis, diphtheria, shigella, Japanese B encephalitis, vancomycin resistant enterococcus, meningococcal meningitis, rubella and infectious mononucleosis, with less than a third of the sample providing a correct response.--------- Conclusions: Results suggest that knowledge of aetiology and transmission of infectious disease is generally poor amongst paramedics. A comprehensive in-service education infection control programs for paramedics with emphasis on infectious disease aetiology and transmission is recommended.

A medical data reliability assessment model

There is currently a strong focus worldwide on the potential of large-scale Electronic Health Record (EHR) systems to cut costs and improve patient outcomes through increased efficiency. This is accomplished by aggregating medical data from isolated Electronic Medical Record databases maintained by different healthcare providers. Concerns about the privacy and reliability of Electronic Health Records are crucial to healthcare service consumers. Traditional security mechanisms are designed to satisfy confidentiality, integrity, and availability requirements, but they fail to provide a measurement tool for data reliability from a data entry perspective. In this paper, we introduce a Medical Data Reliability Assessment (MDRA) service model to assess the reliability of medical data by evaluating the trustworthiness of its sources, usually the healthcare provider which created the data and the medical practitioner who diagnosed the patient and authorised entry of this data into the patient’s medical record. The result is then expressed by manipulating health record metadata to alert medical practitioners relying on the information to possible reliability problems.