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

在缅甸，肝细胞癌的早熟发展是一个紧迫的问题。作为一个可能的原因，铁从环境中超标是有牵连的。在本研究中，我们研究了铁在肝细胞癌组织中的沉积及其与细胞增殖和细胞死亡的关系。为了收集组织样本，我们与医学研究部(DMR/下缅甸)合作。在研究期间，我们3次(2004年12月23-28日、2005年12月15-20日和2007年2月19-23日)访问仰光，新获得37例丙型肝炎病毒阳性病例。在这次访问中，我们不仅与DMR和医科大学的科学家举行了会议，还举办了各种组织化学技术的湿法实验室课程，共有84名医学研究人员参加了这些课程，获得了良好的声誉。此外，我们还于2007年2月20日与长崎大学签订了《缅甸卫生部医学科学司与下缅甸医学研究中心学术合作协议》，以促进…的发展当对27个新获得的肝细胞癌组织标本进行铁沉积检查时，发现缅甸肝细胞癌中有显著的铁沉积，与日本患者不同。此外，我们还发现，有铁沉积的病例Ki-67标记指数明显较高。虽然我们在部分肝细胞癌标本中发现了Fas-Fas配体相关的TUNEL阳性细胞，但其出现频率与铁沉积无明显相关性。此外，在研究铁负荷大鼠肝部分切除后的肝再生时，DNA合成的峰值明显提前，DNA合成的开始与肝细胞中KGF和KGFR的表达暂时相关。此外，我们在CC14处理的铁超载大鼠中也发现了类似的现象。这些结果有力地表明，在病毒感染等诱导肝细胞增殖的条件下，铁超载加速了肝细胞的增殖，可能促进了肝细胞癌的发展。较少

The precocious development of hepatocellular carcinoma (HCC) is an emergent problem in Myanmar. As a possible cause, iron overtaken from the environment is implicated. In the present study, we investigated deposition of iron in the HCC tissues and its correlation with cell proliferation and cell death. To collect the tissue samples, we cooperated with Department of Medical Research (DMR/Lower Myanmar). During the research term, we visited Yangon 3 times (December 23-28, 2004, December 15-20, 2005 and February 19-23, 2007) and newly obtained 37 specimens of HCV positive cases. In our visit, we held not only meetings with DMR and Medical University scientists, but also wet-lab courses on various histochemical techniques in which totally 84 medical researchers took part with a good reputation. In addition, we established the Agreement of Academic Cooperation between DMR/Lower Myanmar, Department of Medical Sciences, Ministry of Health and Nagasaki University on February 20, 2007 to promot … More e our collaboration.When 27 specimens of the newly obtained HCC tissues were examined for iron deposition, a significant deposition of iron in Myanmar HCC was found, not like that of Japanese patients. Moreover, we found that the cases with iron deposition had significantly higher Ki-67 labeling indices. Although we found Fas-Fas ligand related TUNEL positive cells in some H CC specimens, the frequency was not correlated significantly with iron deposition. Further, when we investigated liver regeneration after partial hepatectomy in iron-overloaded rat model, the peak of DNA synthesis was put forward significantly and the onset of DNA synthesis was associated temporarily with the expression of KGF and KGFR in hepatocytes. Also, we found the similar phenomena in CC14 treated iron-overloaded rats. These results strongly indicate that accelerated proliferation of hepatocytes by overloaded iron may promote the development of HCC under the conditions to induce hepatocyte proliferation such as viral infection. Less