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例行胰腺切除术的胰腺浸润性导管癌（invasive ductal carcinoma， IDC）中受体酪氨酸激酶c-kit （KIT）蛋白和TGF-β1的免疫组化表达。统计分析临床病理因素与TGF-β1、KIT表达的相关性。因此，我们报道了在KIT（+）患者中，TGF-β1（+）组的生存率明显优于TGF-β1（-）组，且KIT和TGF-β1的表达对辅助化疗的疗效均无显著影响（Nio Y， Toga T等）。抗癌杂志，25(5):3523- 30,2005)。2006年，我们分析了99例IDC患者肿瘤中orotate磷酸核糖基转移酶（OPRT）活性与临床病理状态和预后之间的关系，特别是其与尿嘧啶和替加富（UFT）、环磷酰胺（CPA）和/或吉西他滨辅助化疗疗效的相关性。因此，我们报道了OPRT（+）组的生存率明显高于OPRT（-）组。在OPRT（+）组中，接受辅助化疗（ACT）联合UFT、CPA或GEM的患者的生存率显著高于未接受ACT的患者；然而，在OPRT（-）组中，ACT（+）组和ACT（-）组的生存率没有差异（Nio Y， Toga T等）。肿瘤学报告，2007,in press)此外，我们研究了11个胰腺癌肿瘤的胸腺苷酸合成酶（TS）的免疫组化表达和TS-mRNA的量，发现核TS的表达与mRNA的量显著相关。细胞核TS表达也与作为细胞增殖指标的MIB-1表达显著相关。我们继续研究肿瘤中TS和PI活性之间的关系，并进一步研究PI与p53、Smad 4和BCL-2之间的关系。在上述免疫组织化学分析中，我们使用半自动方法使用数字视觉计算机程序Image-Pro Plus （IPP）计数核阳性细胞。宏被用来帮助计数核阳性细胞的自动任务。我们为一项发明向岛根大学提出了这个宏观IPP菜单，并被采纳。我们还在第29届技术研究年会上（冈崎会议中心，2007年2月15日）公布了IPP宏菜单和MIB-1免疫组织化学染色方法方案。关于Smad 4基因，我们在2007年3月1日的技术研究大会（名古屋大学技术中心）上报道了其无义介导的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