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Title: The effects of neoadjuvant chemotherapy in human osteosarcoma
Author: Shnyder, Steven David
ISNI:       0000 0001 3407 0291
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1995
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Samples of osteosarcoma examined upon resection or amputation following pre-operative (neoadjuvant) chemotherapy show areas which are "histologically altered", and are neither totally necrotic nor viable. Although the existence of these areas has been acknowledged by several workers, nothing has been published characterising these areas, in order to assess the prognostic indications of these "altered" areas. The object of the present study was to characterise the nature of these "altered" regions in terms of morphology of chemotherapy-affected cells, differences in extracellular matrix molecules, metabolic status of affected cells, changes in expression of the multi-drug resistance molecule P-glycoprotein, and the recovery potential of affected cells. Histological examination revealed a very heterogeneous morphology to osteosarcoma, with six distinct histological sub-classes being recognised. In the "altered" regions enlarged cells similar in morphology to "viable" tumour cells were evident in addition to enlarged cells with degenerative changes, and "viable" tumour cells. Immunohistochemically, it was found that the expression of glycosaminoglycans epitopes was more pronounced in "altered" than in viable regions. Histochemical assessment of cell death revealed that there were significantly more cells, including the enlarged ones, undergoing cell death in "altered" areas than in viable. Expression of proliferating cell nuclear antigen was also found to be greater in "altered" areas, but was only seen in the "viable" cells, and not the enlarged ones. Immunohistochemical detection of P-glycoprotein revealed that there was a significant decrease in the expression of the epitope after surgery compared with at biopsy. In assessing the in vitro recovery potential of "altered" cells in a drug-free environment, no differences were seen between outgrowth of cells from explants of "altered" tissue compared with viable. In conclusion, "altered" areas do not show a good prognostic indication, since any "viable" cells present in these areas may still have the potential to propagate the tumour.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine