ISSN:0378-584X    

DOI:10.1159/000219025

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218888

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218889

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000218890

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

摘要:

Familial adenomatous polyposis (FAP), an autosomal-domi-nant precancerous condition of the colorectum, is caused by mutations in the tumor suppressor gene APC. The detection of germ line mutations in FAP patients allows a reliable presymp-tomatic identification of persons at high risk for FAP within their families. Early diagnosis and adequate surgical therapy definitely improves the prognosis. So far, several genotype-phenotype relationships have been worked out regarding the severity of the disease or the presence of characteristic ocular lesions in relation to the site of mutation in the APC gene. However, there exists considerable phenotypic variation even among patients of the same family. Thus, the actual course of the disease may also be influenced by modifier genes, or by dietary or other exogenous factors. Therefore, endoscopic screening procedures in persons at risk, and decisions on the type or time point of prophylactic colectomy in a clinically diagnosed FAP patient must be based mainly on the clinical findings. The knowledge of the mutation type for which a phenotypical correlate has been found, may serve as an additional information when predictive testing, therapeutic procedures or possible complications are considered.

ISSN:0378-584X    

DOI:10.1159/000218891

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000317695

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

摘要:

The investigation of molecular and genetic changes in tumor cells has brought new insights into the evolution of human malignancies. We have focused on the identification and characterization of genetic alterations in gastric tumors. Tight cell-cell adhesion is critical for the maintenance of epithelial differentiation, while destabilization of adhesion favors invasiveness of epithelial cells and thus carcinoma progression. The E-cadherin cell adhesion complex, composed of E-cadherin itself, α-, β-, and γ-catenin, has been shown to play a major role in establishing and maintaining tight cell-cell junctions. E-cadherin and α-catenin expression are downregulated in various human carcinomas. We found E-cadherin mutations in 50% of diffuse-type gastric carcinomas. Loss of the wild-type allele of E-cadherin was detected in the majority of the tumors exhibiting E-cadherin mutations, but was also found in some intestinal-type carcinomas. No mutations in α- and β-catenin cDNA were identified in gastric tumors of both types. An accumulation of mutations based on genetic instability is thought to contribute to tumor development. Microsatellite instability reflects an elevated mutation rate and was shown to be a characteristic feature of tumors in the majority of patients affected with the hereditary nonpolyposis colorectal cancer syndrome. These alterations have also been identified at a lower frequency in sporadic tumors of various organs including gastric carcinomas. Interestingly, we found microsatellite instability at multiple loci in two synchronous tumors of one patient, who in addition also showed a clustering of gastric tumors in his family. This may be indicative for a familial gastric carcinoma syndrome associated with a germline mutation in one of the genes involved in DNA replication accuracy. The clinical implications of all of these findings for therapy, prognosis, diagnosis, and cancer risk assessment are disc

ISSN:0378-584X    

DOI:10.1159/000218892

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

摘要:

Standard treatment of patients with malignant disease has for many years focused on local surgery, radiation, and systemic chemotherapy. Because available therapy has remained unsatisfactory for the more frequent cancers, oncologists have been forced to explore novel therapeutic approaches. The recognition of existing genetic differences between normal and malignant cells as well as progress in immunology, molecular and cellular biology have made preclinical development and clinical application of a variety of gene therapeutic strategies possible, which are highlighted in this article.

ISSN:0378-584X    

DOI:10.1159/000218893

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

ISSN:0378-584X    

DOI:10.1159/000317696

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger

摘要:

Mutations in the p53 tumor suppressor gene are involved in the molecular pathogenesis of adenocarcinomas in Barrett’s esophagus in approximately 50% of patients. They occur at an early stage of tumor development presumably prior to the development of invasive cancer in premalignant Barrett’s epithelium. The majority of mutations are transition-type mutations, which is in striking contrast to esophageal squamous cell carcinomas and favors a different molecular pathogenesis for the two types of esophageal cancer. A prospective long-term study in a substantial number of patients with benign Barrett’s esophagus is mandatory to finally elucidate the role of p53 mutations as a marker for the malignant potential of Barrett’s epi

ISSN:0378-584X    

DOI:10.1159/000218894

出版商:S. Karger GmbH    

年代:1997

数据来源: Karger