Loss of heterozygosity and homozygous deletion of the tpr locus in human gastric cancer.

BACKGROUND: Despite being one of the world's most common neoplasias, there is little information on the molecular events that lead to gastric cancer. Molecular studies have shown that inactivation of tumor suppressor genes by mutation and/or allelic loss is an important genetic alteration in the multistep process of tumorigenesis. METHODS: In an attempt to identify a putative tumor suppressor gene involved in the carcinogenesis of gastric cancer, we performed Southern blot analysis using the tpr probe for 44 patients with gastric cancer, using tumor tissue and normal tissue from the same specimen. RESULTS: Of the 44 samples, 7 (16%) were informative, heterozygous cases for the tpr probe. Three of the informative cases showed a loss of heterozygosity and 3 cases showed homozygous deletion for the tpr probe (6 of 7; 85%). CONCLUSIONS: These findings suggest that tpr gene plays a role in gastric tumorigenesis, and this may be due to a tumor suppressor effect for the tpr gene.

Chemotherapy in esophageal cancer.

Esophageal cancer is a virulent malignancy, with the conventional approach of surgery or radiation therapy offering patients only a small chance for long-term disease-free survival. The frequent early systemic dissemination of disease has prompted an ongoing interest in the study of chemotherapy. A broad range of antitumor agents have been studied which demonstrate moderate antitumor activity. A number of combination chemotherapy regimens, mainly cisplatin-based, have been studied, which have consistently greater antitumor activity in local regional disease compared with metastatic disease. The use of preoperative chemotherapy in the surgical treatment of the disease remains investigational. Results from clinical trials comparing radiation therapy alone with concurrent radiation and chemotherapy demonstrate a survival benefit for the use of a combination of concurrent chemotherapy and radiation compared to radiation therapy alone. However, current studies with conventional chemotherapy, radiation and surgery are likely to impart at best a modest to moderate improvement in the treatment of esophageal carcinoma. The priority in chemotherapy trials, therefore, remains the identification of new active chemotherapy agents. The search for novel therapeutic approaches, exploiting advances in understanding of the molecular biology of the disease, continues.