The role of SPARC in intestinal extracellular matrix changes and carcinogenesis

炎症性肠病(IBD)、克罗恩S病(CD)和溃疡性结肠炎(UC)是终生、慢性、不可治愈的疾病，全球被诊断为这些疾病的患者数量正在增加。近年来，已经有新的治疗方法的发展，有效地控制了许多此类患者的慢性肠炎。然而，没有证据表明这些疗法可以降低肠道疤痕的发生率或使这些情况复杂化的肠癌的发展。肠炎的愈合可能会导致疤痕形成。是否形成疤痕取决于组织产生和破坏之间的平衡。如果产量超过破坏，那么就可能会留下疤痕，但如果这种平衡能够被改变，有利于减少产量，那么，潜在地，愈合可能会继续进行，而不会留下疤痕。该项目旨在研究一种名为SPARC的蛋白质的作用，该蛋白质可以调节瘢痕的形成，以及它与其他蛋白质的相互作用，这些蛋白质可以改变慢性肠炎小鼠模型中的瘢痕形成。肠道的慢性炎症也会导致结肠癌的发展。结肠癌是澳大利亚人口中最常见的癌症之一。结肠癌初次手术时SPARC水平可预测疾病复发的风险。这项研究的目的是确定SPARC水平是否可以识别那些癌症复发风险较高的患者。SPARC的作用也将在结肠癌的小鼠模型中进行检验，以确定SPARC水平的增加是增加还是降低癌症生长和扩散的速度。

The inflammatory bowel diseases (IBDs), Crohn s disease (CD) and ulcerative colitis (UC), are lifelong, chronic, incurable conditions and the number of patients being diagnosed with these conditions is increasing worldwide. Over recent years there has been the development of new treatments effective in controlling the chronic inflammation of the bowel in many of these patients. There is no evidence, however that these therapies reduce the rate of bowel scarring or the development of bowel cancer that complicated these conditions. Healing of the bowel inflammation can result in scarring. Whether scarring develops or not hinges on the balance between tissue production and destruction. If production outstrips destruction then scarring may occur, but if this balance can be modified in favour of reduced production then, potentially, healing may proceed without scarring. This project aims to investigate the role of a protein, SPARC, that can regulate scar formation and its interactions with other proteins that can alter scar formation in a mouse model of chronic bowel inflammation. Chronic inflammation of the bowel can also cause the development of colon cancer. Colon cancer is one of the most common cancers in the Australian population. The level of SPARC in the colon cancer at time of initial surgery may predict the risk of disease recurrence. The aim of this study is to determine if SPARC levels can identify those patients at higher risk of cancer recurrence. The role of SPARC will also be examined in a mouse model of colon cancer to determine if increased SPARC levels increased or decrease the rate of cancer growth and its spread.