Biomedical subjects
Publications and source records attributed to D A Rew.
Deinococcus radiodurans (DeiRa) is a remarkable organism. Its properties of extreme resistance to environmental damage and ionising radiation command the attention of the cancer research community for the insights which it may bring to the understanding of cytotoxic and radiotherapy treatment resistance.
This article reports the arising from the recent publication of the mouse genome.
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AIM: In vivo labelling of human colonic and rectal tumours with bromodeoxyuridine (BrdUrd) and analysis by flow cytometry (FCM) allows the labelling index (LI), S phase duration (Ts) and the potential doubling time (Tpot) of the tumour to be estimated in vivo. METHODS: The data for a series of 100 tumour specimens from 97 patients with colonic and rectal carcinoma was reported in 1991, and correlated with Dukes' classification and histological differentiation. RESULTS: This study reports the eventual outcome of the 97 patients after 12 years. There were no significant associations between proliferation data of the index tumours and patient outcome. No adverse events were identified which could be attributed to the use of the halogenated pyrimidine label in vivo. CONCLUSION: Dynamic cell proliferation indices provide detailed information on the cell kinetics of colorectal tumours but these do not correlate with clinical prognostic markers or outcome.
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BACKGROUND: The evaluation of the safety of drugs and other chemicals is an important aspect of toxicology work. The mouse micronucleus assay is a standard in vivo genotoxicity assay. Chromosomal damage is an indicator of genotoxicity, which manifests in the formation of micronuclei in polychromatic erythrocytes from bone marrow and in peripheral blood erythrocytes. The assay is laborious to perform by manual counting. The laser scanning cytometer allows automated and rapid quantitation of cellular and subcellular fluorescence in monodisperse cell samples on a microscope slide. The object of this study was to evaluate the application of this new technology in the mouse micronucleus genotoxicity assay. Materials and Methods One hundred forty-four mice of various strains were dosed with combinations of carcinogens and antioxidants. Duplicate blood films were prepared 3 days later. One set of slides was stained with acridine orange, and the proportion of micronucleated erythrocytes was counted in 5,000 cells per slide. The duplicates were stained with propidium iodide (40 microg/ml). Five thousand cells per sample were examined using a laser scanning cytometer. The proportion of micronucleated erythrocytes was measured. RESULTS: A coefficient of correlation of 0.96 was found between the data from the two assays. The automation of the assay on the LSC produced a considerable time saving and efficiency gain. CONCLUSIONS: We conclude that with further development, laser scanning cytometry is likely to become the preferred modality for the performance of standard genotoxicity assays.
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The genome of the fruit fly has recently been sequenced, prior to the release of the human genome sequence within the next few years. The fly has some 13 600 genes, compared with the estimated 80 000 genes in the human genome. Some 70% of genes appear to be broadly conserved across eukaryotic species, and some remarkable homologies have been found between 177 genes in the fly and the 289 human genes so far associated with diseases in man. The fruit fly genome is likely to prove an elegant model and a rich source of experimentation for the aetiology and regulation of human cancers.
Mitochondrial DNA is a small, well characterized chromosome which is transmitted across the generations in the maternal lineage, independently of nuclear DNA. mtDNA acts in effect as a robust, species specific biological clock and tracer which can be used to follow the evolution and spread by geographic migration of populations from their origins. Mutations in mtDNA cause specific maternally hereditable diseases, and can be used for forensic purposes. They are not specifically implicated in neoplasia, but they may provide clues as to the nature and origins of cancer susceptibility in various populations.
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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.
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.
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.
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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.
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.