Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carcinoma in ulcerative colitis (UC) develops from dysplastic precursor lesions, which include flat dysplasia (FD) and polypoid dysplasias (PD). PD may present as single or multiple polypoid structures or as plaque-like lesions that, independent of histological grade, are an indication for colectomy. PDs are histologically similar to adenomas and may not be readily distinguished by light microscopy. It is not known whether FD and PD are different entities, or whether they represent etiologically similar lesions with different morphological expression. We microdissected 25 cases of UC with PD and 19 samples of FD with surrounding chronic colitis (CC) in UC. Loss of heterozygosity (LOH) at the von Hippel Lindau (vHL) gene locus and the putative tumor suppressor genes APC, INK4A (9p16), and p53 was studied. LOH of the vHL gene, INK4A (9p16), and APC was also studied in 11 sporadic adenomas of the colon. LOH at the vHL locus was present in 50% of the samples of PD and in 12% of the samples of FD. LOH was seen in CC close to PD and FD in 26% and 12% of cases, respectively. No adenoma showed LOH of the vHL gene markers studied. LOH in p53 was seen in PD in 16% cases and in FD in 42% cases and in CC close to PD and FD in 0% and 14% cases, respectively. LOH patterns between PD and FD of the markers for APC and 9p16 were not different. LOH in APC was seen in two of five cases of adenoma. We conclude that PD and FD share genetic alterations in APC and 9p16 genes. More frequent involvement of the VHL gene in PD and surrounding CC and involvement of p53 in HGD and CC in FD may represent genetic differences between the development of PD and FD and may be the cause of the different morphology. The infrequency of LOH at the vHL locus in adenomas versus PD may serve as a discriminator between adenomas and PD in diagnostically problematic cases.
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PMID:Loss of heterozygosity of the von Hippel Lindau gene locus in polypoid dysplasia but not flat dysplasia in ulcerative colitis or sporadic adenomas. 974 12

With the high prevalence of gastroesophageal reflux-like symptoms in the United States and the association between GERD symptoms and the premalignant condition of BE, there is more and more demand for new and efficacious techniques to treat BE. A wide variety of endoscopic mucosal ablative techniques have been developed with promising initial results. Long-term control of neoplastic risk, however, has not been demonstrated, and most studies demonstrate that there is still potentially some intestinal mucosa present underneath squamous mucosa. Currently, more study is needed to determine which patient groups require therapy of any kind and to determine which therapies would be the most efficacious. Genetic markers may aid in identification of subgroups that are at risk for cancer and help to identify those who would respond to mucosal therapy. Even in patients who have HGD, subgroups of patients who have focal HGD have been found to have better prognosis than those who have more widespread HGD. Currently, there is sufficient information to consider mucosal ablative techniques in patients who are not good surgical candidates. Photodynamic therapy, APC, KTP, Nd:YAG and argon lasers, MPEC, and EMR may provide good alternatives, depending on the degree of dysplasia, the extent of disease, and the age of the patient. Photodynamic therapy and Nd:YAG laser therapy have been applied to more neoplastic lesions, whereas KTP:YAG, APC, and multipolar coagulation have been successful in nondysplastic Barrett's mucosa. In the future, there will be more information to justify the application of mucosal ablative therapy in selected patients.
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PMID:Role of mucosal ablative therapy in the treatment of the columnar-lined esophagus. 1190 29