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Effect of iron as an environmental poisonous compound upon the precocious development of human hepatocellular carcinoma in Myanmar

铁作为一种环境有毒化合物对缅甸人肝细胞癌早熟的影响

基本信息

批准号：
13576001
负责人：
KOJI Takehiko
金额：
$ 8.32万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

The precocious development of hepatocellular carcinoma (HCC) is a crucial problem in Myanmar. As a possible cause, iron incorporated from the environment is implicated. In the present study, we investigated the deposition of iron and the expression of iron-responsive element binding protein (IREBP) in the tissue sections from Myanmar HCC, and then the correlation between these iron-related parameters and HCC cell kinetics under the intimate cooperation with Department of Medical Research (DMR). Actually, we collected cancerous and non-cancerous parts of more than 30 HCC patients at our 3-times visit to Yangon (December 18 to 24, 2001, December 19-28, 2002 and December 18-23, 2003). During our visit, we also' held not only several meetings with DMR and Medical University scientists and but workshops on TUNEL in 2002 and nonradioactive in situ hybridization in 2003 in DMR, which successfully promoted our friendships. When Myanmar HCC tissue sections were examined for iron deposition, we found significantly heavier deposition of iron in Myanmar HCC than that of Japanese one. However, we failed to analyze the expression of IREBP effectively because of the inevitable loss of structural details after microwave retrieval of reactivity. In the study on the HCC cell kinetics, the specimens with a high proliferating activity assessed by Ki-67 staining was correlated with a low frequency of TUNEL positive cells while low proliferative cases were with frequent apoptosis. In the latter case, an apparent association with Fas ligand expression was found. Moreover, when we investigated the liver regeneration kinetics after partial hepatectomy in iron-overloaded rat model, a significant precocious starting of regeneration was observed, accompanying overall increase in the rate of apoptosis. These results indicate that acceleration of hepatocyte turnover by overloaded iron may promote the development of HCC under the proliferation-induced conditions such as viral infection.

肝细胞癌（HCC）的过早发展是缅甸的一个关键问题。作为一个可能的原因，铁从环境中纳入牵连。在本研究中，我们研究了铁沉积和铁反应元件结合蛋白（IREBP）的表达在组织切片从缅甸肝癌，然后这些铁相关参数和肝癌细胞动力学之间的相关性下，与医学研究部（DMR）的密切合作。实际上，我们在仰光的三次访问中（2001年12月18日至24日，2002年12月19日至28日和2003年12月18日至23日）收集了30多名HCC患者的癌性和非癌性部分。在访问期间，我们不仅与DMR和医科大学的科学家举行了几次会议，而且在DMR举办了2002年的TUNEL和2003年的非放射性原位杂交研讨会，成功地促进了我们的友谊。当缅甸HCC组织切片检查铁沉积时，我们发现缅甸HCC中的铁沉积显著高于日本HCC。然而，我们未能有效地分析IREBP的表达，因为微波反应性恢复后不可避免地丢失了结构细节。在HCC细胞动力学研究中，Ki-67染色评估的高增殖活性的标本与低频率的TUNEL阳性细胞相关，而低增殖的病例与频繁的凋亡相关。在后一种情况下，Fas配体的表达明显的关联被发现。此外，当我们调查了部分肝切除后的铁超载大鼠模型的肝再生动力学，观察到一个显着的早熟开始再生，伴随着整体的凋亡率增加。这些结果表明，在增殖诱导的条件下，如病毒感染，铁超载加速肝细胞更新可能会促进HCC的发展。