Project/Area Number |
11470050
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Human pathology
|
Research Institution | Tottori University |
Principal Investigator |
ITO Hisao Tottori University, Faculty of Medicine, Dep. of Pathology, Professor, 医学部, 教授 (60127610)
|
Project Period (FY) |
1999 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥6,100,000 (Direct Cost: ¥6,100,000)
|
Keywords | apoptosis / p53 gene / FAS / intratumoral microvessel density / signal transduction / Caspase / ARPP / minichromosome maintenance-2 / 消化器癌 / Cydooxygenase-2 / FAS遺伝子 / ARPP遺伝子 / C22ORF2 / Thymidine phosphorylase / MCM2 / PKC / 胃癌 / 大腸癌 / 温熱 / エタノール |
Research Abstract |
1) Apoptotic index of the tumor cells and intratumoral microvessel density (IMVD) showed a significant correlation in human esophageal, gastric and colonic carcinomas. 2) Adenovirus-mediated transfer of wild-type p53 gene resulted in apoptosis (MKN-1), cell arrest (MKN-45, 74 and KATO-III), and non-effectiveness (TMK-1 and OCUM-2M), regardless of p53 gene status. Upregulation of BAX might correlate with apoptosis of MKN-1 cells. 3) FAS and FAS-ligand variably expressed in human esophageal and gastric precancerous lesions and carcinomas, in which apoptosis occurs via FAS-dependent and -independent pathway. Upregulation of FAS-ligand correlated with the progression of the human gastrointestinal carcinomas. No aberration of FAS gene was confirmed in human gastrointestinal carcinomas. Signal transduction through FAS occurs via mitochondria pathway. 4) Gastrointestinal carcinomas variably expressed thymidine phosphorylase and/or cyclooxygenase-2(COX-2), both of which significantly caused increase of IMVD and decrease of apoptosis of the tumor cells. 5) A novel ankirin repeated protein ARPP, consisted 333 a.a. was cloned from the human esophageal carcinoma cell line, TE-1. ARPP expressed in normal skeletal and cardiac muscle, as well as various gastrointestinal carcinoma cell lines. ARPP might play a significant role to inhibit apoptosis. 6) DNA-replication regulating factor, minichromosome maintenance-2(MCM2) is a new, reliable marker for the rapid detection of proliferating cells in normal and neoplastic tissues.
|