A study on the expression of various molecular targets and the efficacy of targeting therapies in human pancreatic cancer

2005年，我们对91例接受胰腺切除术的胰腺浸润性导管癌（IDC）中受体酪氨酸激酶c-kit（KIT）蛋白和TGF-β1的表达进行了免疫组化研究。统计分析TGF-β1和KIT表达与临床病理因素的相关性。结果，我们报道在KIT（+）患者中，TGF-β1（+）组的生存率明显优于TGF-β1（-）组，KIT和TGF-β 1表达对辅助化疗的疗效均无显著影响（Nio Y，Toga T等，Anticancer Res.25（5）3523-30，2005）。在2006年，我们分析了肿瘤中乳清酸磷酸核糖转移酶（OPRT）的活性与99名IDC患者的临床病理状态和预后之间的关联，特别是关于其与使用尿嘧啶和替加氟（UFT）、环磷酰胺（CPA）和/或吉西他滨（ ...更多信息 GEM）。结果，我们报道OPRT（+）组的生存率明显优于OPRT（-）组。在OPRT（+）组中，接受UFT、CPA或GEM辅助化疗（ACT）的患者生存率显著高于未接受ACT的患者;然而，在OPRT（-）组中，ACT（+）和（-）组之间的生存率没有差异（Nio Y，Toga T等人，Oncology Repots，2007，出版中）此外，我们研究了胸苷酸合成酶（TS）的化学表达和TS-11例胰腺癌细胞核TS mRNA的表达与mRNA的表达量呈显著相关。核TS表达与作为细胞增殖指标的MIB-1表达也呈显著相关。本研究采用免疫组化半自动计数法，应用Image-Pro Plus（IPP）数字图像分析软件，对肿瘤组织中TS活性与PI的关系进行了研究，并进一步探讨了PI与p53、Smad 4、BCL-2的关系。利用宏来帮助自动化计数核阳性细胞的任务。我们向岛根大学提出了用于发明的IPP的宏菜单，并且该建议被接受。我们还在第29届技术研究年会（冈崎会议中心，2007年2月15日）上公布了IPP的宏菜单和MIB-1免疫组织化学染色方法的协议。关于Smad 4基因，我们在技术研究大会（名古屋大学技术中心，2007年3月1日）上报告了其无义介导的mRNA衰变。少

In 2005, we investigated immunohistochemical expression of receptor-tyrosine kinase c-kit (KIT) protein and TGF-β1 in invasive ductal carcinoma (IDC) of the pancreas in 91 patients who have received pancreatecotomy. And we analyzed statistically the correlations between the clinicopatholological factors and the expression of TGF-β1 and KIT. As a result, we reported that in patients with KIT(+), the TGF-β1(+) group showed a significantly better that for survival rate than the TGF-β1 (-) group and that neither KIT nor TGF-β1expression had a significant effect on the efficacy of adjuvant chemotherapy (Nio Y, Toga T et al. Anticancer Res. 25(5) 3523-30, 2005).In 2006, we analyzed the association between the activity of orotate phosphoribosyl transferase (OPRT) in the tumor, and the clinicopathological status and prognosis of 99 IDC patients, especially regarding its relevance to the efficacy of adjuvant chemotherapy with uracil and tegafur (UFT), cyclophosphamide (CPA) and/or gemcitabine ( … More GEM). As a result, we reported that OPRT (+) group showed a significantly better survival rate than that for the OPRT (-) group. In the OPRT (+) group, the survival rate of the patients, who received adjuvant chemotherapy (ACT) with UFT, CPA or GEM, was significantly higher than that of the patients without ACT; however, in the OPRT (-) group, there was no difference in the survival between the ACT (+) and (-) groups (Nio Y, Toga T et al. Oncology Repots, 2007, in press)Furthermore, we investigated the immunohistochemichal expression of thymidylate synthase (TS) and the amount of TS-mRNA of 11 pancreatic cancerized tumors and found that nuclear TS expression was significantly correlated with the amount of mRNA. Nuclear TS expression was also significantly correlated with MIB-1 expression that was regarded as the index of cell proliferation (PI). Continuously, we investigate the association between the activity of TS and PI in the tumor, and further the association between PI, and p53, Smad 4 and BCL-2.In immunohistochemical analyses mentioned above, we used semi-automatic method to count nuclear positive cells using a computer program for digital vision, Image-Pro Plus (IPP). Macros were utilized to help automated task for counting nuclear positive cells. We proposed this macro menu of IPP for an invention to Shimane University and the proposal was accepted. We also announced both this macro menu of IPP and the protocol on MIB-1 immunohistochemical staining method in the 29th Annual Meeting of Technical Research (Okazaki conference center, Feb. 15, 2007).On Smad 4 gene, we reported about its nonsense-mediated mRNA decay in the General Meeting of Technical Research (Technical Center of Nagoya University, Mar. 1, 2007). Less