2006 Fiscal Year Final Research Report Summary
Multiple organ failure of tumor-bearing rabbits in cancer cachexia is caused by apoptosis of normal organ cells.
Project/Area Number |
16591680
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Osaka City University |
Principal Investigator |
ISHIKO Osamu Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, 大学院・医学研究科, Professor (80137190)
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Project Period (FY) |
2004 – 2006
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Keywords | cancer cachexia / multiple organ failure / apoptosis / VX2 carcinoma / Bax / Bcl-2 |
Research Abstract |
In cancer-bearing animals, we previously demonstrated that skeletal muscle apoptosis may be involved in muscle wasting, and that Bax may play a role in skeletal muscle cell apoptosis at an early stage. In this study, we investigated the occurrence of apoptosis in the liver, kidney, spleen, lung and heart during cancer cachexia as well as the associations between apoptosis and the expressions of Bcl-2, Bcl-xL and Bax proteins. We also examined the relationship between normal organ apoptosis in cancer cachexia and multiple organ failure. We further studied the changes in body weight, lean body mass (LBM), apoptotic index (AI), DNA laddering pattern and expressions of BAX, Bcl-2 and Bcl-xL in the liver, kidney, spleen, lung and heart in VX2 carcinoma-bearing rabbits. In the early stage of tumor bearing (20 days after implantation), the LBM was significantly reduced by 19.06±1.02% in the tumor-bearing group compared to an increase of 1.66±0.83% in the control group. The apoptotic indices of the liver, kidney, lung and spleen in the tumor-bearing group increased by 14.2±1.75%, 25.8±2.00%, 66.67±6.00% and 24.78±3.81%, respectively, and were significantly higher than the corresponding indices in the control group. DNA laddering patterns characteristic of DNA fragmentation were visible on day 50 in the liver, kidney, spleen and lung in the tumor-bearing group. The expression of Bax increased in the tumor-bearing group and coincided with the occurrence of apoptosis. However, no significant changes were noted in the expressions of Bcl-2 and Bcl-xL. These findings suggest the possibility that normal organ cell apoptosis related to Bax not only causes body weight loss but also multiple organ failure in cancer cachexia.
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Research Products
(2 results)