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This research project looks at cancer of the oesophagus. The oesophagus is the tube connecting the mouth to the stomach' when this tube is exposed to acid and bile from the stomach, it can cause a pre-cancerous tissue to develop, called Barrett's oesophagus. This tissue can then develop into oesophageal cancer in a number of patients. The immune system is the system in the body which responds to damage. When bile and acid damage the oesophagus, cells of the immune system travel to the site of injury to try to limit the damage and repair the tissue. These immune cells are attracted to the area of injury by substances produced by the cells of the oesophagus' these substances are called chemokines. The chemokines (and other substances) produced by cells of the oesophagus change as it firstly develops into Barretts oesophagus and then into cancer. Therefore, the immune cells found in the tissue also change. This change in production of chemokines and in immune cells has been shown previously in many other types of cancer. Many oesophageal cancer patients receive a combination of chemotherapy and radiation therapy (CRT) to try to shrink the tumour, followed by surgery to remove it. While some patients have an excellent response to CRT, others have no response, while suffering many side effects. A previous study in our laboratory has identified certain genes in tumours that can predict patients who will have a poor response to CRT. One of these genes was the code for a chemokine called CCL28, which is not normally produced in the oesophagus. CCL28 attracts certain immune cells and is normally produced in the gut, lung tissue and breast. It has been previously shown in lung cells that production of CCL28 can be caused by other substances involved in the response to damage, such as TNF-a and IL-1b. In this project, we will investigate whether exposure of oesophageal tissue to bile and acids results in the production of CCL28, through the substances TNF-a and IL-1b, and that this production increases as the tissue becomes pre-cancerous and then cancerous. CCL28 may then alter the immune cells attracted to the oesophagus. These immune cells may allow the tumour to become resistant to chemoradiation therapy, causing a poor response and stopping the tumour from shrinking. If this is the case, we may be able to target CCL28 with drugs and alter its production. If we can block CCL28 or stop its production, we may be able to improve patients' response to CRT and help them in their cancer treatment.
The development of a pre-cancerous condition called Barrett's oesophagus occurs when the oesophagus is frequently exposed to bile and acid from the stomach. When this occurs, cells of the immune system travel to the site of injury to try to limit the damage and repair the tissue. These immune cells are attracted to the area of injury by substances produced by the cells of the oesophagus called chemokines. The chemokines produced by cells of the oesophagus change as it firstly develops into Barrett's oesophagus and then into cancer. Therefore, the immune cells found in the tissue also change. The aim of this project is investigate whether exposure of oesophageal tissue to bile and acids results in the production of the chemokine CCL28 and if production of this chemokine increases as the tissue becomes pre-cancerous and then cancerous. In addition, this project aims to understand the role of the chemokine CCL28 in the response of oesophageal cancer patients to chemotherapy and radiation therapy (CRT).
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