BACKGROUND Although the role of p53 in the evolution and prognosis of gastric cancer(GC)has been extensively examined,the exact mechanism of action is incompletely understood.In the last years,p53-target genes were su...BACKGROUND Although the role of p53 in the evolution and prognosis of gastric cancer(GC)has been extensively examined,the exact mechanism of action is incompletely understood.In the last years,p53-target genes were supposed to be involved in the p53 pathway.One of them is the tumor-suppressor gene Maspin,which codifies the protein with the same name.Maspin activity depends on its subcellular localization.To our knowledge,the possible role of TP53 gene in Maspin subcellular localization,in GC cells,has not yet been studied in a large number of human samples.AIM To evaluate the possible role of wild-type and mutated p53 in Maspin subcellular localization.METHODS The present study included 266 consecutive patients with GC in which TP53 gene status,and mutations in exons 2 to 11,respectively,were analyzed and correlated with immunohistochemical expression of p53 and Maspin.RESULTS None of the 266 cases showed mutations in exon 9.The rate of TP53 mutations was 33.83%.The mutation rate was slightly higher in distally-located GCs,with a lower degree(≤5 buds/high power fields)of dyscohesivity(P<0.01).The wildtype cases had a longer survival,compared with mutant GCs,especially in patients without lymph node metastases,despite the high depth of tumor infiltration(P=0.01).The Dukes-MAC-like staging system was proved to have the most significant independent prognostic value(P<0.01).The statistical correlations proved that TP53 gene mutations in exon 7 might induce knockdown of Maspin,but wild-type p53 can partially restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells.CONCLUSION Downregulated Maspin might be induced by mutations in exon 7 of the TP53 gene but wild-type p53 can partially restore nuclear Maspin expression.These findings should be proved in experimental studies.展开更多
Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpres...Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.展开更多
基金the Romanian National Authority for Scientific ResearchNo.20 PCCF/2018。
文摘BACKGROUND Although the role of p53 in the evolution and prognosis of gastric cancer(GC)has been extensively examined,the exact mechanism of action is incompletely understood.In the last years,p53-target genes were supposed to be involved in the p53 pathway.One of them is the tumor-suppressor gene Maspin,which codifies the protein with the same name.Maspin activity depends on its subcellular localization.To our knowledge,the possible role of TP53 gene in Maspin subcellular localization,in GC cells,has not yet been studied in a large number of human samples.AIM To evaluate the possible role of wild-type and mutated p53 in Maspin subcellular localization.METHODS The present study included 266 consecutive patients with GC in which TP53 gene status,and mutations in exons 2 to 11,respectively,were analyzed and correlated with immunohistochemical expression of p53 and Maspin.RESULTS None of the 266 cases showed mutations in exon 9.The rate of TP53 mutations was 33.83%.The mutation rate was slightly higher in distally-located GCs,with a lower degree(≤5 buds/high power fields)of dyscohesivity(P<0.01).The wildtype cases had a longer survival,compared with mutant GCs,especially in patients without lymph node metastases,despite the high depth of tumor infiltration(P=0.01).The Dukes-MAC-like staging system was proved to have the most significant independent prognostic value(P<0.01).The statistical correlations proved that TP53 gene mutations in exon 7 might induce knockdown of Maspin,but wild-type p53 can partially restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells.CONCLUSION Downregulated Maspin might be induced by mutations in exon 7 of the TP53 gene but wild-type p53 can partially restore nuclear Maspin expression.These findings should be proved in experimental studies.
基金Supported by A Grant in Aid for Scientific Research (2001407, 22659072, 22590356, 22790378, 221S0001) from the Ministry of Education, Culture, Sports, Science and Technology of Japana Grant in Aid for the 3rd anti-Cancer from the Ministry of Health, Labour and Welfare (H22-017) and from the Smoking Research Foundation
文摘Ever since its discovery two decades ago,the erythro- poietin-producing hepatoma (EPH)-EPHRIN system has been shown to play multifaceted roles in human gastroenterological cancer as well as neurodevelopment.Overexpression,amplif ication and point mutations have been found in many human cancers and many investigators have shown correlations between these up-regulationsand tumor angiogenesis.Thus,the genes in this family are considered to be potential targets of cancer therapy.On the other hand,the down-regulation of some members as a result of epigenetic changes has also been reported in some cancers.Furthermore,the correlation between altered expressions and clinical prognosis seems to be inconclusive.A huge amount of protein-protein interaction studies on the EPH-EPHRIN system have provided a basic scheme for signal transductions,especially bi-directional signaling involving EPH-ERPHRIN molecules at the cell membrane.This information also provides a manipulative strategy for harnessing the actions of these molecules.In this review,we summarize the known alterations of EPH-EPHRIN genes in human tumors of the esophagus,stomach,colorectum,liver and pancreas and present the perspective that the EPH-EPHRIN system could be a potential target of cancer therapy.