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

1)肝细胞癌侵袭性复发的预测因素和新分子靶点的确定：肝癌患者的预后取决于复发模式，预后指标是肿瘤分化、肿瘤大小和极光激酶B(ARKB)，后者在基因组不稳定中起关键作用。2)细胞间缝隙连接通讯的临床意义，Conexin(CG)43：3)Cx43被发现促进肝癌的生长，并可能是一个分子靶点，维生素K2还被发现通过上调Cx32和下调Cx43.4)抑制肝癌的生长。3)发现与肝癌发生和发展相关的基因：我们发现CREB3L4、INTS3、SNAPAP位于1Q21.5)胰腺癌转移相关基因的鉴定：我们鉴定了与FAK磷酸化的GR7，从而诱导细胞侵袭。我们合成了一种抑制GRB7磷酸化的多肽G7-18NatE-P，从而阐明了其对胰腺癌腹膜转移模型的抑制作用。6)抑制IκB激酶对胰腺癌的作用：在异种移植瘤模型中，发现siRNA和合成的化合物IMD-0354抑制了胰腺癌的生长。

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.