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The mechanism of malignancy associated changes Wilton, David William


Malignancy Associated Changes (MAC) can be defined as subtle morphologic and or physiologic changes which occur in ostensibly normal cells of patients harboring malignant or pre-malignant lesions. This phenomenon has been postulated to have great potential as a powerful tool in the fight against cancer. Recent evidence indicates that this phenomenon can be used in the detection of cancers in their earliest stages, for the objective diagnosis and prognosis of these cancers, as well as a means for monitoring of treatment outcome. Yet the mechanism of MAC remains poorly understood. There have been two main theories proposed to explain the mechanism of MAC. The first, commonly referred to as the "Field Cancerization Theory", postulates that MAC simply reflect mutations in the normal tissue surrounding the tumor resultant from concurrent exposure to carcinogens. If true, this theory implies that there is no clinical value of MAC. The second referred to as the "Humoral Theory of MAC" postulates a direct cause and effect relationship of malignancy to MAC. In this hypothesis, soluble chemical mediators are released from the malignant tissue which act on the normal tissue in the surrounding environment. In these studies an in vitro model was designed to mimic the interaction of malignant cells with normal bronchial epithelial cells. This model was employed to investigate the mechanism of MAC. It was shown that MAC can be induced in vitro demonstrating a cause and effect relationship of malignancy to MAC. Maximal induction of MAC was observed following 48 hours of direct co-culture of tumor cells with normal cells. The strength of MAC expression was found to be dose dependent indicating that this model can be utilized in future studies as a biological assay in the isolation of factors present in malignant conditioned medium capable of inducing MAC. These studies coupled with substantial evidence in vivo provide strong evidence supporting the Humoral mechanism of MAC.

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