AIM: To study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS: Paraffin-embedded tissue samples of 25 patients (18 males and 7 females) with hepatocellu...AIM: To study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS: Paraffin-embedded tissue samples of 25 patients (18 males and 7 females) with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during 2000-2001, and stained using immunohistochemistry method (avidin-biotin-peroxidase) for detection of p53, cyclinD1, RB1, c-fos and N-ras proteins. RESULTS: Six (24%), 5 (20%), 12 (48%) and 2 samples (8%) were positive for p53, cyclinD1, C-fos and N-ras expression, respectively. Twenty-two (88%) samples had alterations in the G1 cell-cycle checkpoint protein expression (RB1 or cyclinD1). P53 positive samples showed a higher (9 times) risk of being positive for RB1 protein than p53 negative samples. Loss of expression of RB1 in association with p53 over-expression was observed in 4 (66.7%) of 6 samples. Loss of expression of RB1 was seen in all cyclinD1 positive, 20 (90.9%) N-ras negative, and 11 (50%) C-fos positive samples, respectively. CyclinD1 positive samples showed a higher (2.85 and 4.75 times) risk of being positive for c-fos and N-ras expression than cyclinD1 negative samples. CONCLUSION: The expression of p53, RB1 and c-fos genes appears to have a key role in the pathogenesis of hepatocellular carcinoma in Iran. Simultaneous overexpression of these genes is significantly associated with their loss of expression during development of hepatocellular carcinoma.展开更多
重组人细胞毒性T细胞相关抗原(Cytotoxic T Lymphocyte Associated Antigen 4,CTLA-4)是一类重要的基因工程药物,其在毕赤酵母中表达水平偏低使其一直无法广泛应用于临床治疗.而影响毕赤酵母中的外源蛋白分泌表达的因素,主要为内质网中...重组人细胞毒性T细胞相关抗原(Cytotoxic T Lymphocyte Associated Antigen 4,CTLA-4)是一类重要的基因工程药物,其在毕赤酵母中表达水平偏低使其一直无法广泛应用于临床治疗.而影响毕赤酵母中的外源蛋白分泌表达的因素,主要为内质网中的折叠速率以及不可折叠蛋白积累造成的胞内胁迫压力.本文通过在毕赤酵母细胞中过表达HAC1基因对毕赤酵母细胞中未折叠蛋白反应(Unfolded Protein Response,UPR)的信号通路进行调控,从而改善了CTLA-4蛋白的表达水平.摇瓶中改造菌株M-HAC1发酵上清液中该蛋白的分泌表达量是原始菌株表达量的2.55倍.展开更多
文摘AIM: To study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS: Paraffin-embedded tissue samples of 25 patients (18 males and 7 females) with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during 2000-2001, and stained using immunohistochemistry method (avidin-biotin-peroxidase) for detection of p53, cyclinD1, RB1, c-fos and N-ras proteins. RESULTS: Six (24%), 5 (20%), 12 (48%) and 2 samples (8%) were positive for p53, cyclinD1, C-fos and N-ras expression, respectively. Twenty-two (88%) samples had alterations in the G1 cell-cycle checkpoint protein expression (RB1 or cyclinD1). P53 positive samples showed a higher (9 times) risk of being positive for RB1 protein than p53 negative samples. Loss of expression of RB1 in association with p53 over-expression was observed in 4 (66.7%) of 6 samples. Loss of expression of RB1 was seen in all cyclinD1 positive, 20 (90.9%) N-ras negative, and 11 (50%) C-fos positive samples, respectively. CyclinD1 positive samples showed a higher (2.85 and 4.75 times) risk of being positive for c-fos and N-ras expression than cyclinD1 negative samples. CONCLUSION: The expression of p53, RB1 and c-fos genes appears to have a key role in the pathogenesis of hepatocellular carcinoma in Iran. Simultaneous overexpression of these genes is significantly associated with their loss of expression during development of hepatocellular carcinoma.
文摘重组人细胞毒性T细胞相关抗原(Cytotoxic T Lymphocyte Associated Antigen 4,CTLA-4)是一类重要的基因工程药物,其在毕赤酵母中表达水平偏低使其一直无法广泛应用于临床治疗.而影响毕赤酵母中的外源蛋白分泌表达的因素,主要为内质网中的折叠速率以及不可折叠蛋白积累造成的胞内胁迫压力.本文通过在毕赤酵母细胞中过表达HAC1基因对毕赤酵母细胞中未折叠蛋白反应(Unfolded Protein Response,UPR)的信号通路进行调控,从而改善了CTLA-4蛋白的表达水平.摇瓶中改造菌株M-HAC1发酵上清液中该蛋白的分泌表达量是原始菌株表达量的2.55倍.
