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Biomedical subjects

D A Rew

Publications and source records attributed to D A Rew.

At least 19 recordsLinked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

Objective quantitative analysis of eosinophils and bronchial epithelial cells in induced sputum by laser scanning cytometry.

BACKGROUND: Sputum induction is an important non-invasive technique for measuring airway inflammation in asthma. Cell numbers are often too low for flow cytometric analysis. Laser scanning cytometry (LSC) is a novel technique that allows objective multicolour fluorescence analysis of cells on a microscope slide. METHODS: LSC was used to determine sputum eosinophil and bronchial epithelial cell counts. We first confirmed that we could measure eosinophil counts accurately in peripheral blood using alpha-major basic protein (MBP) immunofluorescent staining. Sputum induction was performed according to standard protocols. Sputum samples from eight normal controls and 12 asthmatic patients were analysed by LSC and manual counting by two independent observers. Octospot cytospins were fixed and stained with mouse-alpha-human-MBP monoclonal antibody or mouse-alpha-human-cytokeratin antibody and goat-alpha-mouse Oregon Green conjugated second antibody. RESULTS: Sputum induction provided a mean (SE) of 0.99 (0.2) x 10(6) cells per donor. More than 3000 cells on three cytospins per slide were analysed per cell type. The intraclass correlation coefficient (R) and standard deviation (SD) of differences in eosinophils determined by manual counting and LSC were 0.9 and 2.1, respectively, and for bronchial epithelial cell counts they were 0.7 and 2.0. Selective detection of labelled cells was confirmed visually after relocation. CONCLUSION: Eosinophils and bronchial epithelial cells can be accurately and reproducibly counted in an objective manner. LSC is therefore a potentially powerful new method for immunophenotyping leucocytes and epithelial cells objectively in induced sputum in patients with asthma.

Asthma↗
PubMed1998

Comparison of flow and laser scanning cytometry for the assay of cell proliferation in human solid tumors.

The introduction of the laser scanning cytometer offers new capabilities in cell proliferation research, through its capacity for validation of each and every cell event through direct visualization on the microscope slide. In this study, we report a direct comparison of proliferation data derived from flow and laser scanning cytometry of human tumor nuclei labeled in vivo with bromodeoxyuridine (BrdUrd). Nuclear suspensions from 19 invasive ductal breast carcinomas and 12 gastric adenocarcinomas were prepared and analysed for BrdUrd uptake and DNA content. Specimens were analysed using a FACScan and then prepared on cytocentrifuge preparations for laser scanning cytometry. DNA index, labeling index (LI), duration of S-phase (Ts) and potential doubling time (Tpot) were calculated using standard procedures. There was an excellent correlation between the two techniques in the calculation of DNA index (R = 0.983, P > 0.0001) and LI (R = 0.924, P > 0.0001). The Ts proved more problematical (R = 0.448, P = 0.0115) but the Tpot showed closer agreement (R = 0.851, P > 0.0001) as the LI was the dominant determinant of Tpot. No single parameter could be identified as the major source of variation between the two techniques. We conclude that the laser scanning cytometer produces data equivalent to that obtained by flow cytometry.

Adenocarcinoma↗
PubMed1998

Image analysis enhancement of the laser scanning cytometer.

The laser scanning cytometer offers a range of novel applications and the capacity for direct visual validation of experiments through sample analysis on a microscope slide. Linkage of the instrument to an image analysis system through standard connections and software enhances the capabilities of the instrument in image capture and manipulation. In this technical note, we describe a simple linkage between the LSC and the Kontron KS100 Image Analysis System, an example of a standard commercial image processing instrument.

Image Cytometry↗
PubMed1998

Campaign strategy and tactics for clinical trials in surgical oncology.

The strategic planning of the campaign against cancer and the employment of clinical trials on a national and supranational basis could be improved. Lessons and principles derived from other spheres of ordered activity might be usefully applied to the realm of clinical trials. Principles taught by military strategists may find practical applications in the development and prosecution of successful clinical trials of cancer therapy. In this paper we reflect upon the parallels and divergences between the principles of campaign strategy needed for the successful prosecution of military objectives and the efficient and effective prosecution of major clinical trials.

Clinical Trials as Topic↗