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Biomedical subjects

D A Rew

Publications and source records attributed to D A Rew.

At least 37 records · Page 2Linked to original sources

DNA microarray technology in cancer research.

Microarray technology transforms the study of functional genetics. The entire genomic activity of cells and tissues can be analysed and compared on single slides, or gene chips. In cancer research, this will allow the better understanding of the regulation of activity of cells and tumours in various states. It will also allow the classification of individual tumours by their gene expression patterns, which may also describe and predict therapeutic resistance and sensitivity patterns. This short article provides a short introduction to the technology and its applications.

Animals↗

The European Journal of Surgical Oncology and its contribution to cancer surgery.

This article describes the European Journal of Surgical Oncology, the EJSO, its aims and objectives, and its conventional and electronic publishing strategy. It highlights the role of the journal in publishing original work and educational content in respect to the generality of the clinical and academic disciplines comprising modern surgical oncology. The journal is in a steady expansion phase with a growing impact factor, and the editorial team aims to consolidate its place in the premier league of specialist journals through the merit and quality of its content and publication standards.

Europe↗

Modelling in tumour biology part 1: modelling concepts and structures.

Our strategies for the treatment of cancer are constrained by our incomplete understanding of tumour biology and behaviour, and by the enormous complexity and resilience to therapeutic perturbation found in the biological world. We are obliged to simplify this complexity through the use of models and mechanistic explanations. In the first of these papers, we consider the nature of modelling mechanisms available to clinical researchers and the extent to which we rely upon them in our understanding of the nature and behaviour of tumours. In the second part, we will consider specifically how models help us to develop more effective strategies for cancer therapy.

Algorithms↗

Cell production rates in human tissues and tumours and their significance. Part 1: an introduction to the techniques of measurement and their limitations.

In the past two decades, the technology of laser cytometry and use of the halogenated thymidine (HP) analogues bromodeoxyuridine and iododeoxyuridine as proliferation labels, have allowed us to quantify the rate of cell turnover in tissues and tumours, in clinical samples as in laboratory models. The principal studies have used injection of bromo- or iododeoxyuridine to measure cell production rates in vivo. Flow cytometry (FCM) has been used to estimate the S phase labelling index (LI) and the S phase duration (Ts) and calculate the cell production rate, represented by the potential doubling time (Tpot). This has allowed calculation of time-dependent indices of proliferation from single biopsies of HP pulse labelled human tissues and tumours. In the first part of this two-part review, we describe the technique and its limitations as a biological assay. The second part summarizes the knowledge gained about cell production rates and the relevance that this information may have to future investigative, prognostic and treatment strategies.

Bromodeoxyuridine↗

Cell production rates in human tissues and tumours and their significance. Part II: clinical data.

This paper reviews the available data for cell production rates of human tissues and tumours, measured in vivo using halogenated pyrimidine labelling and laser cytometry. The technique has now been widely evaluated, and we draw general inferences from the proliferative data over a broad range of tumour and tissue types. Estimates of the S-phase duration, the time taken for DNA synthesis in cycling cells, are consistent over a narrow range with a median value of around 10 hours, notwithstanding the constraints of the experimental and statistical technique, in normal tissues and tumours. This suggests that Ts values may be a species-specific constant. The more easily measured labelled S-phase fraction, or labelling index, shows much greater intra and intertumour variation within any one tumour class. It may thus be a surrogate for time dependent measurements to a first order approximation. The cell production rate, described by the potential doubling time (Tpot), is remarkably rapid in most tumours, a median value of the order of 5 days, and much faster than clinical volume doubling times for most lesions. The rapid cell production rates in normal tissues and tumours highlight the importance of cell loss in the growth and modelling of biological structures. Cell production rate measurements do not adequately describe the biological aggressiveness of tumours. They may be used to refine adjuvant strategies for radiotherapy and chemotherapy in experimental research. Dynamic halogenated pyrimidine labelling has provided unique and valuable insights into the living biology of human tissues and tumours.

Adenocarcinoma↗

Breast substitution.

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Attitude of Health Personnel↗

EDUCATIONAL SECTION: risk analysis in surgical oncology-part I: concepts and tools.

All clinical procedures invoke risk. Many interventions in cancer management carry a particularly high element of risk, expressed through morbidity and premature death. Formal risk analysis is a discipline which is fundamental to engineering, to finance, to the airline industry and many other sectors of public life. Clinical risk analysis involves risk prediction, risk management and risk avoidance. Risk analysis is rarely invoked or taught in the clinical sciences, and management appraisals on individual patients almost never include a formal estimate of risk. Clinical decisions tend to be guided by qualitative judgements, and by the personality interactions of patients and clinicians. A formal evaluation of risk on a case by case and procedural basis might reduce morbidity and cost in surgical oncology practice. This article introduces the concepts, the spectrum and history of risk analysis and the tools for risk prediction.

Humans↗

Risk analysis in surgical oncology-part II: risk and the practising surgeon.

Surgery for cancer imparts a high risk of morbidity and premature mortality. Inappropriate decisions and inadequate information can have a profound effect on the outcome of interventions. A formal process of appraisal of options, aided by modern information technology, may help rationalize and improve management stratagems and reduce risk. Rigorous and obsessional attention to risks in clinical and surgical procedures and processes, including the selection and training of surgeons, process and human reliability analysis, and ubiquitous error reduction strategies will also help minimize risk. These approaches will have a significant bearing on familiar surgical practice and will need to be extended across the multidisciplinary spectrum of cancer care.

Decision Making↗

Clinical outcome and bromodeoxyuridine-derived proliferation indices in 75 invasive breast carcinomas.

INTRODUCTION: In vivo labelling of human breast tumours with bromodeoxyuridine (BrdUrd) and analysis by flow cytometry (FCM) allows the labelling index (LI), S phase duration (t(s)) and the potential doubling time (t(pot)) of the tumour to be estimated. METHODS: The data for a series of tumour specimens from 75 patients with invasive breast carcinoma were reported in 1991, correlated with their lymph-node status, tumour size and grade. RESULTS AND CONCLUSIONS: This study reports the follow-up data over 10 years in respect of time to recurrence and death from the disease. There were no significant correlations between proliferation data and outcome measures. No adverse events were identified which could be attributed to the use of the halogenated pyrimidine label in vivo.

Adult↗

Modelling in surgical oncology--part III: massive data sets and complex systems.

Human tumours are complex and unstable biological systems. New intellectual and mathematical approaches together with massive computing power are transforming our capacity to model and investigate such complexity. Computers also allow massive data sets to be collated and analysed. Such sets include the medical and epidemiological records of entire populations; the entire genetic code of the human being and of other species, including parasites and disease vectors; and the genotype of each and every individual. Massive data sets take us into new dimensions of complexity for which simple linear mathematics are insufficient. The analysis of the grades of complexity which determine protein and cell construction, cell to cell interactions within tissues and organs, the morphogenesis of entire organisms and population interactions with disease vectors require the sophisticated mathematical tools of non-linear analysis, neural networks, chaos and complexity theory. The capacity for closer representations of reality through powerful computational models also allows us to look afresh at the generalizations of conventional statistics. Within this computational cauldron, we may also find help in the better understanding of oncogenesis and cancer therapy. This paper, the third in our series on modelling in tumour biology, considers the breadth of opportunity and challenge at the interface between cell biology and biomathematics.

Computational Biology↗

Part IV. The 20th century: the maelstrom of progress.

<<The last decades of the 19th century were occupied with the detailed study of the morphology of tumours, the separation of the varieties of disease, the elucidation of histogenesis and the writing of the natural history of malignant diseases. The twentieth century opens as the experimental era. It seems likely to become noteworthy as the period of specific aetiological investigations which promise to widely separate many neoplastic diseases formerly held to be closely related. It may, thereby, prove to be the era of successful therapeutics and prophylaxis.

Humans↗