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Title: Modulating the inflammatory response towards cancer in Zebrafish
Author: Antonio, Nicole
ISNI:       0000 0004 5921 197X
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Surgery is a key cancer therapy and is still the most effective method to treat human solid cancers, which have not yet metastasized. However, tissue damage is thought to trigger development of various cancers, provide a favourable niche for tumour reoccurrence, and facilitate the growth of pre-existing micro-metastases suggesting that surgery may have clinical consequences other than removal of the primary cancer. The zebrafish, Danio rerio, has emerged as an excellent model organism in which to study cancer cell biology. I have undertaken live imaging studies of neutrophil and macrophage interactions between wounds and pre-neoplastic RasG12V lesions in Zebrafish larvae, and show that the immune cells recruited to the wound are quickly drawn out from the wound by competing signals from pre-neoplastic cells. The increased exposure to innate immune cells leads to increased proliferation of preneoplastic cells, which I show is entirely dependent upon innate immune cells, and at least in part, due to PGE2 derived from the immune cells. I then extended this study into adult zebrafish expressing RasG12V, where melanoma development appears to be accelerated after chronic tissue wounding. While chronic infections, with accompanying inflammation, can lead to malignant changes over time, there is evidence that acute, febrile infections may be cancer preventative. I have investigated whether the introduction of a foreign immune stimulus - bacteria - in larvae can shift the polarisation of the innate immune system towards a defensive and cytotoxic response leading to inhibition of pre-neoplastic cell proliferation. This work was influenced by the century-old work of Dr. William Coley who successfully treated cancer patients by deliberately infecting patients and inducing a high fever.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available