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1.
Bignold LP 《Cellular and molecular life sciences : CMLS》2002,59(6):950-958
Almost all solid malignancies exhibit complex cytological and architectural abnormalities, which vary from cell to cell and
area to area within the same tumour, and between tumours of the same type. The degrees of these abnormalities do not correlate
perfectly with the biological behaviour (especially growth rate and metastatic potential) among the various tumour types.
These features of tumours have long been considered to invalidate simple mutational or 'abnormal gene expression' (epigenetic)
theories of carcinogenesis. The 'mutator phenotype/clonal selection' hypothesis is based on the now well-established phenomenon
of genetic instability of cancer cells, and proposes that this instability is an essential requirement for the development
of tumours, and not an irrelevant side-effect of some other process. This paper argues that this hypothesis can provide a
satisfactory explanation for the diverse histological and biological features of solid malignancies. Further, because virtually
all solid tumours are histologically abnormal, genetic instability is likely to be essential for the malignant process. The
concepts of mutator phenotype and clonal selection are therefore supported.
Received 8 April 2002; accepted 25 April 2002 相似文献
2.
L. P. Bignold 《Cellular and molecular life sciences : CMLS》1987,43(8):860-868
Summary Diverse cell types, including Amoebae, leukocytes, embryonic cells and tumour cells move about on solid surfaces to accomplish such activities as feeding, bacterial destruction, embryological development and metastasis. Theories of the mechanism of this movement are reviewed and a model is proposed which invokes the existence of specific, laterally mobile, transmembranous structures in the cell membrane, which are reversibly adhesive for both the contractile apparatus of the cell internally, and the substratum externally. By this model, the movement of all these cell types can be explained. 相似文献
3.
L P Bignold 《Experientia》1988,44(6):518-521
The motile responses of human polymorphonuclear leukocytes (PMN) to N-formyl-methionyl-leucyl-phenylalanine (FMLP) in the Boyden chamber using a new sparse-pore polycarbonate membrane (pores 3 micron in diameter and occupying 0.1% of surface area) were compared with those demonstrated by using a standard polycarbonate (Nuclepore) filtration membrane (pores 3 micron in diameter and occupying 5% of surface area). Motility of PMN in gradients of FMLP using the new membrane was not influenced by chemokinetic effects of the factor, and the 'background' migration of the cells was minimal. However, motility of PMN in gradients of FMLP using the standard membrane was found to be influenced by chemokinetic effects of the chemotactic factor, and the 'background' or 'control' migration (in the absence of chemotactic factor) of the cells was substantial. Greater directional migration of PMN according to steepness of the gradient of chemotactic factor was demonstrated with the use of the new membrane. The new membrane may be of considerable value in the further study of the chemotactic responses of PMN. 相似文献
4.
Summary Enhanced vascular permeability induced in synovialis of the rat by histamine and serotonin lasts 5–15 min and that induced by bradykinin less than 5 min. Synovialis of the rat becomes refractory to the permeability effects of repeated doses of each of these substances in the hour following initial application.This work was carried out while L.P.B. was supported by a Medical Postgraduate Scholarship from the National Health and Medical Research Council of Australia. 相似文献
5.
6.
L. P. Bignold 《Cellular and molecular life sciences : CMLS》1995,51(4):317-327
Eosinophil leukocytes have been studied for over 100 years, with various theories being advanced of the mechanism of their recruitment and function, especially in relation to the lesions of allergy, asthma and parasitism. Early notions of recruitment and function depended on observations of the cells in inflammatory lesions, while later theories have used additional information from in vitro studies. Many issues are still unresolved. This review aims to cover the older and more recent literature of the mechanisms of accumulation of eosinophil leukocytes and their functions, with a view to illuminating the controversies and difficulties of research in the area. 相似文献
7.
L. P. Bignold 《Cellular and molecular life sciences : CMLS》1988,44(6):518-521
Summary The motile responses of human polymorphonuclear leukocytes (PMN) to N-formyl-methionyl-leucyl-phenylalanine (FMLP) in the Boyden chamber using a new sparse-pore polycarbonate membrane (pores 3 m in diameter and occupying 0.1% of surface area) were compared with those demonstrated by using a standard polycarbonate (Nuclepore) filtration membrane (pores 3 m in diameter and occupying 5% of surface area). Motility of PMN in gradients of FMLP using the new membrane was not influenced by chemokinetic effects of the factor, and the background migration of the cells was minimal. However, motility of PMN in gradients of FMLP using the standard membrane was found to be influenced by chemokinetic effects of the chemotactic factor, and the background or control migration (in the absence of chemotactic factor) of the cells was substantial. Greater directional migration of PMN according to steepness of the gradient of chemotactic factor was demonstrated with the use of the new membrane. The new membrane may be of considerable value in the further study of the chemotactic responses of PMN. 相似文献
8.
Bignold LP 《Cellular and molecular life sciences : CMLS》2003,60(5):883-891
The mutator phenotype theory of carcinogenesis suggests that genetic instability is an early and essential part of tumour development. This instability provides for substantially random cell-to-cell genomic variation (genomic heterogeneity) to arise among cells of individual tumours. Genetically unstable cells then produce 'successful' clones of cells with the necessary mutations for malignant behaviour. In a previous paper (Bignold L. P., Cell. Mol. Life Sci. 2002; 59: 950-958), it was pointed out that a population of cells which is heterogeneous for behaviour-related genes may well also be heterogeneous for morphology-related genes. This would result in cellular pleomorphism among cells of individual tumours, and so explain this almost universal characteristic of solid malignancies. paragraph sign If the concept of random genomic variability applies fully to the histopathology of tumours, then most tumours should show a mixture of neoplastic features, especially nuclear atypia, loss of specialised function (such as loss of production of mucus by glandular cells) and invasiveness. However, occasional lesions might be expected to occur which show these characteristics independently. That is, lesions should exist which exhibit one or two of the three characteristics of neoplasms without the other(s). paragraph sign This paper identifies, among human tumours, lesions which show independence of these characteristics. Two of the examples discussed are a Bowenoid solar keratosis that shows severe nuclear atypia, but no apparent loss of specialisation and no invasiveness. On the other hand, anaplastic small cell carcinoma of the lung often exhibits marked loss of differentiation, very aggressive invasion and metastasis, but little nuclear pleomorphism. paragraph sign These examples are considered to provide further support for the importance of the mutator phenotype to the pathogenesis of neoplasia. 相似文献
9.
Bignold LP 《Cellular and molecular life sciences : CMLS》2003,60(6):1107-1117
Genetic instability in tumours results in cell-to-cell variability of genome which parallels the cell-to-cell variability of microscopic morphology and of behaviour (tumour cell heterogeneity) of these lesions. Genetic instability is therefore strongly supported as the fundamental process by which normal tissue cells become neoplastic. The commonest current suggestion for the mechanism of initiation of carcinogenesis is a 'direct hit' mutation of a 'cancer critical' gene in a somatic cell by carcinogenic agents. However, this mechanism does not account for the activity of carcinogens which are not mutagens, and does not explain why many mutagens are not carcinogens. This paper proposes a nonmutational (nongenotoxic) mechanism of initiation of genetic instability in previously normal cells as follows: 1) During S phase of local tissue stem cells, carcinogen binds to and disables the proofreading enzyme for a new DNA strand. 2) While it is disabled, the proofreading enzyme fails to correct illicit changes in the nucleotide sequence(s) for one or more genes for proofreading fidelity or repair of DNA in the new strand of DNA, which passes to one daughter cell. 3) When this daughter cell is a continuing stem cell, the resulting cell line remains immortal, and retains its prior differentiation commitment to produce daughter cells of a particular type. However, the acquired genetic instability in this cell line causes secondary mutations which lead to uncontrolled growth, and the heterogeneous morphologic and behavioural features of a tumour resembling the parent cell type. 相似文献
10.
Résumé La perméabilité vasculaire de la membrane synoviale du rat est augmentée par l'histamine, la sérotonine et la bradykinine. Dans cette réaction la sérotonine est plus active que l'histamine et la bradykinine.
L.P.B. is supported by a Medical Postgraduate Research Scholarship from the National Health and Medical Research Council of Australia.
We are indebted to Associate ProfessorJ. Garcia-Lémé, University of São Paulo, Brazil, for advice. 相似文献
L.P.B. is supported by a Medical Postgraduate Research Scholarship from the National Health and Medical Research Council of Australia.
We are indebted to Associate ProfessorJ. Garcia-Lémé, University of São Paulo, Brazil, for advice. 相似文献