The effect of immune stimulation and immune suppression on experimental pre-invasive and early invasive carcinoma of cervix

McDicken, Ian Wilson (1977) The effect of immune stimulation and immune suppression on experimental pre-invasive and early invasive carcinoma of cervix. MD thesis, University of Glasgow.

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This thesis comprises a study of the pre-invasive and early Invasive phases of a chemically Induced carcinoma of uterine cervix, and the effects on the course of development of these of Immune stimulation with Bacille Calmette-Guerin or Immune suppression with anti-lymphocyte serum. The aims of the experiments are to Investigate the effects of immune stimulation or immunosuppression on ; (1) the time from carcinogen implantation to the detection of the first malignant cells by cytology, and (2) the progression or regression of the various stages of pre-malignancy and early malignancy in the suggested progression : normal -> moderate dysplasia -> severe dysplasia and / or carcinoma in-situ -> carcinoma, with and without the continuing presence of the carcinogen. Part I describes the experimental model and the reasons for Its use. The model is a variation of that first described by Murphy in which, in mice, carcinoma of cervix is induced by Inserting a thread, with a knot at one end impregnated with a carcinogen-beeswax mixture, through the cervical canal so that the impregnated knot rests against the cervix. The main reasons for using this model are : - (1) It gives a more reproducible Incidence of tumours In the cervix than other methods, such as painting with carcinogen. (2) The development of the lesions can be followed and staged by the use of exfoliative cytology. This allows B.C.G. or A.L.S. to be given at a stage in the development when some definite pathological change in the progression to malignancy can be demonstrated. This avoids the necessity of giving the agents blindly, or the complications that might arise from the use of traumatic biopsy as a means of estimating the stage of development. (3) To reduce the complications due to the presence of the carcinogen, such as any immunosuppressive effect, the thread can be cut and the carcinogen removed. This also minimises any continuing carcinogenic effect such as might occur in short duration experiments in which large doses of carcinogen are given, with the result that the carcinogenic effect continues after the effect of immune stimulation has ceased. It also reduces the possibility of a massive carcinogenic effect overwhelming more subtle alterations in the immune status. Part I also describes the experimental design which essentially consists of two groups of experiments, in the first of which the carcinogen remains in position throughout the experiment and in the second of which the carcinogen is removed as soon as the first cytologically malignant cells are detected. A.L.S. or B.C.G. are given when, in individual mice, a recognised stage in the development of carcinoma is reached. Part II reviews the literature regarding A. L. S. emphasising the variable aspects of its effect on cellular and humoral immune responses to various antigens, and to different types of allografts , in differing strains and species of animals, where these have a bearing on tumour immunity. Also emphasised is the fact that many experiments have been performed without control groups using normal serum, compatible with the A. L.S., so that any toxic or antigenic stimulatory effect of the serum constituents may be missed. Part III reviews the literature regarding B.C.G. and immune stimulation, and emphasises the numerous possibilities for varying immune responses to B.C.G. such as strain differences, preparation differences, and genetic drift in the bacteria, and variable human and animal responses in the recipients, and how these can affect the comparison and interpretation of experimental results. Part IV gives details of the preliminary experiments. Part V gives the results obtained which can be summarised as : There is no alteration in the length of time from the implantation of the carcinogen to the detection of the first cytologically malignant cells in any groups. The length of time from implantation to invasion is little altered in the experimental groups where the carcinogen remains in position but that where the carcinogen Is removed B.C.G. increases and A.L.S. decreases the pre-invasive stage. Where the carcinogen remains in position the epithelium does not revert to normal in any group but remains cytologically malignant. A.L.S. increases and B.C.G. decreases the number of tumours resulting from the pre-invasive stages where the influence of the carcinogen is removed. B.C.G. will arrest the progression of some early invasive lesions, while from this stage, A.L.S. increases the resulting number of tumours, in those experiments where the carcinogen has been removed. Part VI discusses the results in relation to other experiments.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: K A Porter
Keywords: Immunology
Date of Award: 1977
Depositing User: Enlighten Team
Unique ID: glathesis:1977-72275
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 24 May 2019 15:12
Last Modified: 24 May 2019 15:12

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