Detection of dormancy-regulating factors and the related proteins in the proliferation and progression of human gastrointestinal carcinomas

1.in（1）胃腺瘤被认为处于休眠状态。与粘膜内胃癌相比，腺瘤细胞凋亡指数（AI）明显升高，增殖活性明显降低，这可能与肿瘤内微血管密度（IMVD）及胸苷磷酸化酶、环氧化酶（考克斯）-2和P53的表达有关。（2）RUNX 3基因在手术标本和培养细胞系中均表达于胃主细胞、G细胞、食管粘膜表层细胞和肺泡上皮细胞，而在食管癌、胃癌、口腔癌和支气管癌中表达较低。(3)A新近证实的ARPP基因在包括心肌在内的肌肉中表达，并且表达随去神经而降低。（4）考克斯-2在口腔癌、食管癌、胃癌、支气管癌及MFH中的表达与IMVD、AI及Skp 2表达相关。（5）胃癌、结肠癌和胆囊癌中Fhit表达与Mlh 1表达相关，而与P53表达及早期癌变无关。（1）RUNX 3基因转染可使胃癌细胞周期阻滞，但不引起凋亡。carcinomas.2.in（2）考克斯-2选择性抑制剂可抑制食管癌和胃癌细胞的增殖和细胞周期阻滞，但不能诱导细胞凋亡。（3）Fas诱导的细胞凋亡信号转导通过线粒体途径进行，并受PI 3 K-Akt激活的影响。PI 3 K-Akt抑制剂增强肿瘤细胞的增殖。3.其他（1）制备ARPP和RUNX 3的特异性抗体以及RUNX 3表达载体。ARPP基因敲除小鼠成功制备。

1.in vivo analysis(1)Gastric adenomas are considered to be in dormancy. Comparing with the intramucosal gastric carcinomas, the adenomas showed significantly higher apoptotic index (AI) and lower proliferative activity, which might correlated with intratumoral microvessel density(IMVD) and the expression of thymidine phosphorylase、cyclo-oxygenase(COX)-2、and P53.(2)RUNX3, a possible tumor suppressor gene, was demonstrated to express in gastric chief cells and G ells, as well as superficial cells of esophageal mucosa and lung alveolar cells, in contrast to obvious lower expression in esophageal, gastric, oral and bronchial carcinomas, in the both operative specimens and cultured cell lines.(3)A newly confirmed ARPP gene showed to express in the muscle including cardiac muscle and the expression was decreased by denervation.(4)Human oral, esophageal, gastric, bronchial carcinomas and MFH showed immunohistochemical expression of COX-2, which correlated with IMVD and AI, as well as Skp2 expression.(5)Fhit expression was correlated with Mlh1, but not P53 expression and early events of carcinogenesis in the gastric, colonic and gall bladder carcinomas.2.in vitro analysis(1)RUNX3 gene transfection resulted in cell cycle arrest, but not apoptosis in the human gastric carcinoma cell lines.(2)COX-2 selective inhibitor caused suppression of cell proliferation and cell cycle arrest, but not apoptosis in the esophageal and gastric carcinoma cell lines.(3)Signal transduction of Fas-induced apoptosis was conducted via mitochondrial pathway, which was affected by PI3K-Akt activation. PI3K-Akt inhibitor enhanced tumor cell apoptosis.3.Others(1)Specific antibodies for ARPP and RUNX3 and RUNX3 expression vector were generated. ARPP knock-out mouse was successfully produced.