Novel strategies for cancer therapy targeting premetastatic niche

针对转移前生态位的癌症治疗新策略

• 批准号: 21390376
• 负责人: KONNO Hiroyuki
• 金额: $ 8.49万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390376/
• 关键词: 消化器悪性腫瘍; 分子標的治療; 転移機構; 悪性化; 網羅的解析; 消火器悪性腫瘍; 転移機序

1. Mechanisms of colorectal liver metastasis : We compared difference in miRNA expression between primary colorectal cancers and their liver metastases using microarray. We focused on miR-122 which was the most up-regulated in liver metastases compared with primary tumors and has been reported as a liver-specific miRNA. Immunohistochemical analysis revealed that expression level of cationic amino acid transporter 1(CAT1), a target gene of miR-122, was significantly lower in liver metastases compared with primary tumors. Furthermore, patients with CAT-1 low primary colorectal cancer had significantly shorter liver metastasis-free survival than the patients with CAT-1 high tumors.2. Lipid alteration in gastric cancer : We compared the lipid content between gastric cancer and its adjacent non-neoplastic mucosa using imaging mass spectrometry and found that potassium-adducted phosphatidylcholine(PC)(16 : 0/18 : 1) was predominantly expressed in cancer lesions. Lysophosphatidylcholine(LPC) is known to be converted to PC in the presence of acyl-CoA by LPCAT1 in Lands' cycle. Immunohistochemical analysis revealed that LPCAT1 was highly expressed in cancer predominantly in differentiated adenocarcinoma. LPCAT1 protein and concomitant lipid alterations in gastric mucosa appear to be involved in the carcinogenic or developmental process of gastric cancer.

1. 结直肠癌肝转移的机制：我们使用微阵列技术比较了原发性结直肠癌和肝转移灶之间miRNA的表达差异。我们关注的是miR-122，与原发性肿瘤相比，miR-122在肝转移中上调最多，并且已被报道为肝脏特异性miRNA。免疫组化分析显示，miR-122靶基因阳离子氨基酸转运蛋白1（CAT1）在肝转移瘤中的表达水平明显低于原发肿瘤。此外，低CAT-1原发性结直肠癌患者的无转移生存期明显短于高CAT-1原发性结直肠癌患者。胃癌的脂质改变：我们使用成像质谱法比较了胃癌及其邻近非肿瘤性粘膜的脂质含量，发现钾内合磷脂酰胆碱（PC）（16:0 / 18:1）在癌灶中主要表达。已知溶血磷脂酰胆碱（LPC）在有酰基辅酶a存在的情况下通过LPCAT1在Lands循环中转化为PC。免疫组化分析显示，LPCAT1在肿瘤中高表达，主要在分化腺癌中。胃粘膜LPCAT1蛋白及其伴随的脂质改变似乎参与了胃癌的致癌或发展过程。

项目成果

TSU68, an antiangiogenic receptor tyrosine kinase inhibitor, induces tumor vascular normalization in a human cancer xenograft nude mouse model

• DOI: 10.1007/s00595-009-4020-y
• 发表时间: 2009-12-01
• 期刊: SURGERY TODAY
• 影响因子: 2.5
• 作者: Ohta, Manabu;Kawabata, Toshiki;Konno, Hiroyuki
• 通讯作者: Konno, Hiroyuki

Surgical intervention for imatinib and sunitinib-resistant GISTs

对伊马替尼和舒尼替尼耐药的胃肠道间质瘤的手术干预

• 发表时间: 2011
• 期刊: Int J Clin Oncol
• 影响因子: 3.3
• 作者: Kikuchi H;Setoguchi T;Miyazaki S;Yamamoto M;Ohta M;Kamiya K;Sakaguchi T;Konno H
• 通讯作者: Konno H

大腸癌におけるKRASを介したVEGFの低酸素誘導機構

VEGF通过KRAS诱导结直肠癌缺氧机制

• 发表时间: 2011
• 作者: 菊池寛利、今野弘之;他
• 通讯作者: 他

質量顕微鏡を用いた胃癌凍結標本の解析

使用质量显微镜分析冷冻胃癌标本

• 发表时间: 2010
• 作者: 上原隆志、瀬藤光利、今野弘之;他
• 通讯作者: 他

胃癌腹膜播種に対する審査腹腔鏡NBI画像診断を用いた新たな治療戦略

腹腔镜NBI影像诊断胃癌腹膜播散的治疗新策略

• 发表时间: 2010
• 作者: 神谷欣志;太田学;宮崎真一郎;飯野一郎太;上原隆志;瀬戸口智彦;菊池寛利;平松良浩;中村利夫;今野弘之
• 通讯作者: 今野弘之