2002 Fiscal Year Final Research Report Summary
Rationale of hypoxic condition in Development of Liver Cancer
| Project/Area Number |
12670901
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Radiation science
|
|---|
| Research Institution | Wakayama Medical University |
|---|
Principal Investigator |
KISHI Kazushi Wakayama Medical University, Department of Radiology, Assistant Professor, 医学部, 助教授 (70254547)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SATO Morio Wakayama Medical University, Department of Radiology, Assistant Professor, 医学部, 助教授 (80188680)
SATO Morio Wakayama Medical University, Department of Radiology, Professor, 医学部, 教授 (50154109)
SHIRAI Shintaro Wakayama Medical University, Department of Radiology, Fellow, 医学部, 助手 (00192120)
KAKUDO Ken-ichi Wakayama Medical University, 2^<nd> Department of Pathology, Professor, 医学部, 教授 (00112037)
|
|---|
| Project Period (FY) |
2000 – 2002
|
| Keywords | Liver cancer / CCl4 / Wister Rat / Hypoxia induced factor 1alpha / Hypoxia / Hepatitis / Liver cirrhosis / Cox-2 inhibitor |
|---|
| Research Abstract |
The liver is one of the most hypoxia-sensitive and hypoxic organs because of the energy consumptive cellular functions and that the 80% of the blood supply is portal venous flow. The most human liver cancer is known arising from the chronic hepatitis base or cirrhotic base. And several experimental liver cancers in the rat develop among inflammatory regenerative process.
In the present experiment carcinogenetic model applied to Wister rat did not show any evidence of carcinogenesis with repeated injection of CCl4. Instead of the expected carcinogenic process they showed a course of inflammatory reaction and fibrotic reaction that was a common process with the liver cirrhosis. The inflammatory course showed transient hypoxia in the liver parenchyma bottomed at the 4^<th> week followed by V-shaped rebound while the CCl4 was still administrated. Then the rebound was not because the toxin (CCl4) was ceased but supposedly because due to tissue reaction including repairing process such as angiogenesis. This was coincided with the fact that, in the molecular research, this hypoxia was reflected to increase of the HIF1alpha. In the control group and a group in which CCl4 and anti-inflammatory drug (a cox-2 inhibitor) group showed less intensive hypoxia, and the less intensive induction of the HIF1alpha, correspondingly. Though this observation is very limited but is suggesting that inflammatory process involved in carcinogenic condition and that hypoxia is related to severity of inflammation. This also suggest a possibility of a hypothesis that anti-inflammatory drug (especially, cox-2 inhibitor) may be useful in reducing the cancer induction though hypoxic process in the liver. This project will be succeeded with a new budget by the same head investigator.
|
