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

1.(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，这可能与瘤内微血管密度（IMVD）及胸苷磷酸化酶、环加氧酶(COX)-2、P53的表达有关。(2)RUNX3可能是抑癌基因，在胃主细胞、G细胞、食管黏膜浅表细胞和肺泡细胞中均有表达，而在食管癌、胃癌、口腔癌和支气管癌、手术标本和培养细胞系中的表达均明显较低。(3)一个新证实的ARPP基因在包括心肌在内的肌肉中表达，并因去神经支配而表达减少。(4)人口腔癌、食管癌、胃癌、支气管癌和MFH中COX-2的免疫组化表达与IMVD和AI相关，Skp2的表达也与之相关。(5)在胃癌、结肠癌和胆囊癌中，Fhit表达与Mlh1相关，而P53表达与早期癌变事件无关。(1)转染RUNX3基因后，人胃癌细胞系细胞周期阻滞，但未发生细胞凋亡。(2)COX-2选择性抑制剂可抑制食管癌和胃癌细胞株的细胞增殖和细胞周期阻滞，但不导致细胞凋亡。(3) fas诱导细胞凋亡的信号转导是通过线粒体途径进行的，受PI3K-Akt激活的影响。2 . PI3K-Akt抑制剂增强肿瘤细胞凋亡。(1)生成ARPP和RUNX3特异性抗体，生成RUNX3表达载体。ARPP敲除小鼠研制成功。

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.