title: Decreased levels of nitric oxide production and nitric oxide synthase-2             expression are associated with the development and metastasis of hepatocellular             carcinoma.
abstract: Many studies have demonstrated the function of nitric oxide (NO) or nitric             oxide synthase-2 (NOS-2) in cancer as pro-neoplastic or anti-neoplastic effectors,             but the role of NO and NOS-2 in hepatocellular carcinoma (HCC) remains unclear.             The aim of this study was to investigate the levels of NO production and NOS-2             expression in HCC and adjacent non-tumor liver tissues and to clarify whether             the levels of NO/NOS-2 are related to the clinicopathological features of HCC.             The levels of NO production were examined in tumor and adjacent non-tumor liver             tissues of 30 patients with HCC. The expression of NOS-2 was detected by real-time             polymerase chain reaction (RT-PCR) and immunohistochemical analysis in HCC and/or             adjacent non-tumor liver tissues. Mutant p53 and proliferating cell nuclear antigen             (PCNA) were also immunohistochemically investigated in liver tissues. The levels             of NO in HCC were significantly lower compared to adjacent non-tumor liver tissues             (P<0.001). The relative mRNA and protein expression levels of NOS-2 in HCC             were also significantly lower compared to adjacent non-tumor liver tissues (P<0.01             for both). We found that the levels of NO in patients suffering from HCC metastasis             were lower compared to those without metastasis (P<0.05) and NOS-2 expression             was correlated with tumor diameter (P<0.05) and metastasis (P<0.05). In             addition, mutant p53 protein was expressed in the majority of HCC samples and             the proliferation rate of HCC was significantly higher than that of adjacent non-tumor             liver tissues. These data indicate that decreased levels of NO/NOS-2 may partially             contribute to overexpression of the mutant p53 protein and excessive proliferation;             this may be a potential mechanism in the development and progression of HCC.
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical                     College, Huazhong University of Science and Technology, Wuhan 430030,                     P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: De-An
authors.initials: DA
authors.lastname: Tian
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Yu-Zhen
authors.initials: YZ
authors.lastname: Yang
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II