ISSN:0267-1379    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Colon cancer results from the accumulation of genetic alterations. Genomic instability creates a permissive state in which a potential cancer cell is allowed to acquire enough mutations to become a cancer cell. Several forms of genomic instability are common in colon cancer: microsatellite instability (MSI), chromosome instability (CIN), and chromosome translocations. MSI occurs in approximately 15% of colon cancers and results from inactivation of the mutation mismatch repair (MMR) system secondary to either MMR gene mutations or hypermethylation of thehMLH1promoter. It promotes tumorigenesis by generating mutations in target genes that possess coding microsatellite repeats, such as the transforming growth factor-β receptor type II gene. CIN occurs in most other colon cancers and leads to a different pattern of gene alterations that culminate in tumor formation. It seems to result from mutations in genes that control mitosis, DNA damage repair, centrosome structure and function, and other fundamental processes in DNA replication. The clinical significance of genomic instability is now under investigation, and it is hoped that this research will soon yield results that have an immediate effect on the treatment of colon cancer.

ISSN:0267-1379    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Colon carcinogenesis is a multistep process that involves deletions, mutations, and changes in expression of genes that regulate growth, differentiation, and apoptosis. Hyperproliferation can initiate dysplastic growth, resulting in accumulation of genetic defects and progression of colon cancer. Although genetic instability, because of inheritance of specific genetic defects, plays a dominant role in familial cancers, in the majority of sporadic cancers hyperproliferation is likely to play a permissive role in initiation and progression of the disease. Thus factors that regulate growth, differentiation, and apoptosis are likely to play an important role in colon carcinogenesis. Autocrine gastrins, insulin-like growth factor-II, transforming growth factor-&agr;, and endocrine gastrins have been implicated in the tumorigenic potential of colon cancer cells. In this article we focus on the role of endocrine and autocrine gastrins in colon cancer and review recent advances that suggest a role of processing intermediates of gastrin in colon carcinogenesis.

ISSN:0267-1379    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

In this brief review, we focus on some of the proposed mechanisms of injury in peripheral visceral afferents (sensory) pathways and the enteric nervous system, including the interstitial cells of Cajal. Injury involving afferent neurons is discussed because of the relevance of these neurons to the pathophysiology of pain syndromes. The effect of various noxious stimuli on sensory and enteric neural function is examined. Finally, we discuss recent data on the role of autoimmune antibodies in neuronal injury in systemic diseases, such as diabetes mellitus and the Lambert-Eaton myasthenic syndrome. Neither central nervous system manifestations of peripheral nerve injury nor functional bowel disorders are addressed in this review. An improved understanding of the pathophysiology of peripheral neuronal dysfunction will probably result in new treatment strategies for a broad range of gastrointestinal disorders, including constipation, pseudo-obstruction, ileus, and inflammatory bowel disorders.

ISSN:0267-1379    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The term inflammatory bowel disease refers to two chronic, relapsing or remitting, inflammatory disorders of the intestinal tract that although somewhat similar clinically represent two markedly different and distinct disorders histologically, endoscopically, immunologically, and by many other means. The pathogenesis of these diseases, ulcerative colitis and Crohn’s disease, remains unknown and medical and surgical therapy is limited. Approximately 70% of individuals with Crohn’s disease require surgery with another 40% to 45% requiring reoperation, whereas approximately 20% to 25% of patients with ulcerative colitis undergo surgical intervention. This review highlights the specific clinical features of the disease as well as some of the recent insights into the cause of the disease. Standard medical therapy is highlighted and more recent biologic therapies including the use of anti–tumor necrosis factor-&agr; antibodies are described. The changing focus of therapy from nonspecific anti-inflammatory medications to targeted biologic therapies is reviewed. A number of novel therapeutic targets are highlighted and future directions for research and clinical testing are discussed.

ISSN:0267-1379    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

There are few randomized, prospective trials evaluating the optimal diagnostic and therapeutic strategies in the management of lower gastrointestinal bleeding. However, recent data suggest that urgent colonoscopy represents a safe and effective initial diagnostic approach. The role of tagged erythrocyte scintigraphy is yet to be defined, but it may be of utility as a screening test for visceral angiography. Colonoscopy and angiography both offer substantial therapeutic options but remain of unproved benefit from a treatment standpoint; surgery continues to play an important role in the management of lower gastrointestinal bleeding. Obscure gastrointestinal bleeding, which often presents as lower gastrointestinal bleeding, continues to be one of the most challenging diagnostic and therapeutic problems in gastroenterology. Occult gastrointestinal bleeding, often arising from the lower gastrointestinal tract, usually mandates gastrointestinal evaluation.

ISSN:0267-1379    

出版商:OVID    

年代:2000

数据来源: OVID