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

• 批准号: 16406005
• 负责人: KOJI Takehiko
• 金额: $ 8.38万
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16406005/
• 关键词: Myanmar; hepatocellular carcinoma; iron; iron-responsive element binding proteins; hepatitis viruses; apoptosis; electroporation; molecular histochemistry; KGF; 鉄反応エレメント結合蛋白; 分子組織細胞化学

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

肝细胞癌（HCC）的过早发展是缅甸面临的一个新问题。一个可能的原因是从环境中吸收的铁。在本研究中，我们研究了 HCC 组织中铁的沉积及其与细胞增殖和细胞死亡的相关性。为了收集组织样本，我们与医学研究部（DMR/下缅甸）合作。研究期间，我们3次访问仰光（2004年12月23日至28日、2005年12月15日至20日、2007年2月19日至23日），新获取HCV阳性病例标本37例。此次访问，我们不仅与DMR和医科大学的科学家进行了会面，还举办了各种组织化学技术的湿实验室课程，共有84名医学研究人员参加，获得了良好的声誉。此外，我们于2007年2月20日建立了DMR/下缅甸、卫生部医学科学部和长崎大学之间的学术合作协议，以促进我们的合作。当对新获得的27个HCC组织标本进行铁沉积检查时，发现缅甸HCC中有明显的铁沉积，与日本患者的铁沉积不同。此外，我们发现铁沉积病例的 Ki-67 标记指数明显较高。尽管我们在一些 H CC 标本中发现了 Fas-Fas 配体相关的 TUNEL 阳性细胞，但其频率与铁沉积没有显着相关。此外，当我们在铁超载大鼠模型中研究部分肝切除后的肝再生时，DNA合成的峰值显着提出，并且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 治疗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，铁超载导致的肝细胞加速增殖可能促进HCC的发展。较少的

项目成果

Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer

• DOI: 10.1038/labinvest.3700166
• 发表时间: 2004-11-01
• 期刊: LABORATORY INVESTIGATION
• 影响因子: 5
• 作者: Tamaru, N;Hishikawa, Y;Koji, T
• 通讯作者: Koji, T

Expression of keratinocyte growth fector/fibroblast growth factor-7 and its receptor in human lung cancer. correlation with tumour proliferative activity and patient prognosis.

角质形成细胞生长因子/成纤维细胞生长因子7及其受体在人肺癌中的表达。

• 发表时间: 2004
• 期刊: J. Pathol. 204・1
• 作者: Yamayoshi;T.
• 通讯作者: T.

Coexpression of keratinocyte growth factor and its receptor in normal and prostate cancer tissue : Possible formation of autonomous andromedin loop.

角质细胞生长因子及其受体在正常和前列腺癌组织中的共表达：可能形成自主的仙女座环。

• 发表时间: 2004
• 期刊: Acta Histochem Cytochem 37(6)
• 作者: Aoki D;Yamamoto-Fukuda T;Hishikawa Y;Nakamura M;Sakai H;Kanetake H;Koji T.
• 通讯作者: Koji T.

Induction of cell death in rat small intestine by ischemia reperfusion: differential roles of Fas/Fas ligand and Bcl-2/Bax systems depending upon cell types

• DOI: 10.1007/s00418-005-0765-6
• 发表时间: 2005-03-01
• 期刊: HISTOCHEMISTRY AND CELL BIOLOGY
• 影响因子: 2.3
• 作者: An, SC;Hishikawa, Y;Koji, T
• 通讯作者: Koji, T

Adenoviral-mediated gene transfer of IL-13R α2 chain followed by IL-13 cytotoxin treatment offers potent targeted therapy for cytotoxin-resistant cancers.

腺病毒介导的 IL-13R α2 链基因转移随后进行 IL-13 细胞毒素治疗为细胞毒素抗性癌症提供了有效的靶向治疗。

• 发表时间: 2005
• 期刊: Int.J.Cancer, 116(1)
• 作者: Saito;M.;Murata;T.;Watanabe;K.;Kawakami;K.;Suzuki;M.;Koji;T.;Puri;R.K.;Kitazato;K.;Kobayashi;N.
• 通讯作者: N.