Multidisciplinary research for molecular mechanism of cancer progression and development of diagnostic and therapeutic tool

这个研究项目产生了以下结果。1)肝细胞癌（HCC）侵袭性复发的预测因素及新分子靶点的发现：发现HCC患者的预后与复发方式有关，预后指标为肿瘤分化、肿瘤大小和在基因组不稳定性中起关键作用的极光激酶B （aurora kinase B， ARKB）。ARKB被认为是HCC治疗的一个有前景的分子靶点。2)临床意义的差距交界细胞间通信,Conexin (Cg) 43:3)残雪43发现促进肝癌的生长,和可能的分子的目标,同时维生素K 2被发现抑制肝癌的生长通过upregulation Cx32 Cx43.4)的差别,对这些基因的识别肝细胞癌的致癌作用和发展:我们确定CREB3L4 INTS3, SNAPAP位于1 q 21.5)识别胰腺癌转移的基因:我们发现Gr7被FAK磷酸化，从而诱导细胞侵袭。我们合成了抑制Grb7磷酸化的肽G7-18NATE-P，从而阐明了其对胰腺癌腹膜播散模型的抑制作用。6) IKKB激酶（Iκ B kinase， IKKB）抑制胰腺癌的作用：在异种移植模型中发现IKKB抑制剂SiRNA和合成化合物IMD-0354抑制胰腺癌的生长。

This research project yielded the following results.1) Predictive factors for aggressive recurrence of hepatocellular carcinoma (HCC) and identification of a novel molecular target: A prognosis of HCC patients was found to depend on the mode of recurrence, and prognostic indicators were tumor differentiation, tumor size, and aurora kinase B (ARKB) which plays a key role in genome instability. ARKB is considered to be a promising molecular target for HCC treatment.2) Clinical implication of Gap junctional intercellular communication, Conexin (Cg) 43:3) Cx 43 was found to facilitate the growth of HCC, and to be a possible molecular target, and also Vitamin K 2 was found to suppress HCC growth through upregulation of Cx32 and downregulation of Cx43.4) Identification of genes responsible for carcinogenesis and development of HCC : We identified CREB3L4, INTS3, SNAPAP located at 1q 21.5) Identification of genes responsible for pancreatic cancer metastasis : We identified Gr7 which is phospholylated with FAK, thereby inducing cell invasion. We synthesized a peptide, G7-18NATE-P which inhibits phospholylation of Grb7, thereby clarifying the inhibitory effect on the peritoneal dissemination model of pancreas cancer.6) Effect of Iκ B kinase (IKKB) inhibition on pancreas cancer: SiRNA and synthesized compound, IMD-0354 for IKKB inhibitor were found to suppress the growth of pancreas cancer in the xenograft model.