The long-term objective of our research is to contribute to the early detection and prevention of esophageal cancer (EC). We have been conducting long-term studies on the etiology, pathogenesis, and nutritional intervention of esophageal cancers in a high incidence area of Henan Province in northern China. In recent studies on the early molecular events in esophageal carcinogenesis, we have observed p53 protein accumulation and gene mutations in esophageal dysplasia and hyperplasia, and even in near-normal epithelia. In this proposal, we plan to determine the molecular basis for the p53 protein accumulation and the biological consequence of p53 accumulation/mutation in human subjects, and to study other molecular events which are important in esophageal carcinogenesis.
The specific aims of this project are as follows: 1. To determine the molecular basis of p53 accumulation at different stages of esophageal carcinogenesis. Using esophageal biopsy samples and resected tissues from Henan, China, we will test the hypothesis that there are two types of p53 protein accumulation in near-normal and hyperplastic epithelia: one type due to wild-type p53 protein and the other type due to mutant p53 protein; the sites of mutation will be analyzed. 2. To examine the biological consequences of wt p53 elevation and p53 mutations in cell cycle control and related molecular events in esophageal carcinogenesis. For this aim, we will use specific cell cycle markers in multiparameter flow cytometry and cell sorting, and will study the expression of WAF1(Cip1) and other molecular changes. 3. To test, in follow-up studies, the hypothesis that p53 mutation makes the host prone to esophageal carcinogenesis and to explore the practical application of our findings in the early detection and prognosis of EC. Our ability to study molecular changes in human esophageal biopsy samples and to conduct follow-up studies in this high EC risk area enables us to test the above hypotheses directly. The project is expected to provide important new information on the early molecular events in human esophageal carcinogenesis. This information is important for the prevention, early detection, and prognosis of EC not only in this high incidence area but also in other areas, including the United States.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA065871-04
Application #
2895215
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Bledsoe, Marianna
Project Start
1996-05-15
Project End
2000-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Rutgers University
Department
Type
Schools of Pharmacy
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Cai, Yuyang Christine; So, Chi K; Nie, Alex Yan et al. (2007) Characterization of genetic alteration patterns in human esophageal squamous cell carcinoma using selected microsatellite markers spanning multiple loci. Int J Oncol 30:1059-67
An, Ji-Ye; Fan, Zong-Min; Gao, Shan-Shan et al. (2005) Loss of heterozygosity in multistage carcinogenesis of esophageal carcinoma at high-incidence area in Henan Province, China. World J Gastroenterol 11:2055-60
Wang, L-D; Guo, R-F; Fan, Z-M et al. (2005) Association of methylenetetrahydrofolate reductase and thymidylate synthase promoter polymorphisms with genetic susceptibility to esophageal and cardia cancer in a Chinese high-risk population. Dis Esophagus 18:177-84
Fang, Ming Zhu; Chen, Dapeng; Sun, Yi et al. (2005) Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res 11:7033-41
Gao, She-Gan; Wang, Li-Dong; Fan, Zong-Min et al. (2005) Histochemical studies on intestinal metaplasia adjacent to gastric cardia adenocarcinoma in subjects at high-incidence area in Henan, north China. World J Gastroenterol 11:4634-7
So, Chi-Kwong; Nie, Yan; Song, Yunlong et al. (2004) Loss of heterozygosity and internal tandem duplication mutations of the CBP gene are frequent events in human esophageal squamous cell carcinoma. Clin Cancer Res 10:19-27
An, Ji-Ye; Fan, Zong-Min; Zhuang, Ze-Hao et al. (2004) Proteomic analysis of blood level of proteins before and after operation in patients with esophageal squamous cell carcinoma at high-incidence area in Henan Province. World J Gastroenterol 10:3365-8
Wang, Yimin; Fang, Ming Zhu; Liao, Jie et al. (2003) Hypermethylation-associated inactivation of retinoic acid receptor beta in human esophageal squamous cell carcinoma. Clin Cancer Res 9:5257-63
Wang, Li-Dong; Zheng, Shu; Liu, Bin et al. (2003) CYP1A1, GSTs and mEH polymorphisms and susceptibility to esophageal carcinoma: study of population from a high- incidence area in north China. World J Gastroenterol 9:1394-7
Fang, Ming Zhu; Wang, Yimin; Ai, Ni et al. (2003) Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63:7563-70

Showing the most recent 10 out of 21 publications