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

2005年，我们研究了91例胰腺癌患者胰腺组织中受体酪氨酸激酶c-Kit(KIT)蛋白和转化生长因子-β-1的免疫组织化学表达。统计分析不同临床病理因素与转化生长因子-β-1、KIT表达的相关性。因此，我们报道了在KIT(+)患者中，转化生长因子-β-1(+)组的生存率明显好于转化生长因子-β-1(-)组，且KIT和转化生长因子-β1的表达对辅助化疗的疗效均无显著影响(NioY，Toga T等)。2006年，我们分析了99例IDC患者肿瘤中磷酸核糖基转移酶的活性与临床病理状态和预后的关系，特别是它与尿嘧啶和替加氟(UFT)、环磷酰胺(CPA)和/或吉西他滨(…)辅助化疗疗效的相关性更多宝石)。因此，我们报告了OPRT(+)组的存活率明显好于OPRT(-)组。在OPRT(+)组中，接受UFT、CPA或GEM辅助化疗(ACT)的患者的生存率显著高于未接受ACT的患者，而在OPRT(-)组中，ACT(+)组和(-)组之间的生存率差异无统计学意义(Nio Y，Toga T等)。此外，我们还研究了11例胰腺癌组织中胸苷酸合酶(TS)的免疫组织化学表达及TS-mRNA的表达，发现核TS的表达与TS-mRNA的表达呈显著正相关。核TS的表达与作为细胞增殖指标的MIB-1的表达也呈正相关。在上述免疫组织化学分析中，我们使用计算机数字视觉程序Image-Pro Plus(IPP)，采用半自动方法计数核阳性细胞。宏被用来帮助完成核阳性细胞计数的自动化任务。我们向岛根大学提出了这项发明的IPP宏菜单，并被接受了。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的这个宏菜单和MIB-1免疫组织化学染色方法。关于Smad4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)上报道了其无义介导的mRNA衰退。较少

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