Multi-scale Modeling Method Research Of Chronic Inflammation-Cancer Network

Inflammatory bowel disease (IBD) is divided into two types, one kind is that can happen anywhere in the gastrointestinal tract and lead to gastrointestinal tissue progressive destruction of crohn’s disease (CD). Another kind is a disease of unknown etiology, limited rectum and colitis colon mucosa and submucosa of ulcerative colitis (UC). These two diseases causes a huge public health care burden particularly in developed countries and currently there is no effective treatment.Numerous studies suggest that CD and UC results from an abnormal immune response against components of commensal microbiota in genetically susceptible individuals. However, the exact etiology of the disease is not clear. Despite extensive research efforts, understanding of the disease mechanisms at cellular and molecular levels remains elusive. In this work,a network model is developed and simulations are performed using an agent-based network modeling (ABNM) to elucidate the detailed mechanisms of immune response in CD and UC progression. Our modeling study identifies several important positive feedback loops as a driving force for CD and UC initiation and progression.Colorectal cancer (CRC) is a worldwide common digestive tract malignant tumor, along with progress in colorectal cancer, cancer terminal can appear break through the intestinal wall adjacent tissues and organs such as the abdominal cavity,ovarian invasion and lymph nodes, liver, lungs and other tissues of the transfer.There is an upward trend in the worldwide incidence. Inflammatory bowel disease(IBD) is a common chronic inflammation of the intestinal and can occur anywhere in the gastrointestinal tract, causing gastrointestinal gradual destruction of the organization. Experiments prove that patients with IBD will have more chance of CRC, so there was a close link between inflammation and cancer.Chronic inflammation can promote the development and progression of cancer,which is the important process of cancer development. As "the tumor microenvironment (tumor microenvironment, TME)" concept is put forward, from a new perspective on the relationship between inflammation and cancer asked a new understanding. It is now considered by a large number of inflammatory cells and the secretion of various factors, which can promote the local environment for the growth of tumors, and tumor microenvironment can develop and play an important role in the process of transfer,but for "inflammatory carcinoma" in the process of evolution related pathogenesis remains unclear. Despite extensive research efforts,understanding the mechanism of disease at the cellular and molecular levels remain elusive. In this work, the network model and simulate the use of a network model based on agent (ABNM) to clarify the detailed mechanism of the immune response in the CRC-IBD. Our modeling research identified several important positive feedback loop as a driving force of the CRC initiation and development. Calculation results accord with the clinical and laboratory measurements, provide new understanding of the cellular and molecular mechanisms of disease.