慢性肝病患者中雌激素致肝癌作用

雌激素的水平与肝癌的发生相当密切。当然,生理浓度的雌二醇（E2）控制人体的生长发育及第二性征,在生殖内分泌系统中担当重要角色,不会诱发肿瘤。但在慢性肝病患者体内E2浓度长期超出生理范围会对机体产生不利影响,尤其表现在可促进慢性肝病向肝癌转化。临床证实外源性雌激素长期刺激可导致肝细胞肿瘤发病率的升高。 雌激素致肝癌机理相当复杂,E2及其代谢产物均有不同程度的致肝癌作用。E2可促进癌细胞增生。

三种危险因素的协同致肝癌作用

据《中华预防医学杂志》1996年9月第30卷第5期报道 中山医科大学附三院周元平等,为分析黄曲霉毒素B1（AFB1）,乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）在致人原发性肝细胞癌（HCC）时可能的协同作用。

酒精与肝癌发生关系研究现状

近来研究表明,酒精消耗与肝癌有关,本文就此作一综述。 一、流行病学 研究揭示,酒精消耗量与肝癌发病率呈正相关。一项研究显示居住在城市里每天习惯饮酒超过80克酒精且40岁以上的男性发生肝癌的危险性增加。来自启东肝癌高发区的资料发现两个肝癌高、低乡1979～1998年肝癌死亡率分别为51.19/10万与20.44/10万(P【0.01)。

Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice

AIM:To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model,and to determine the con-tribution of adiponectin defi ciency to colorectal cancer development and proliferation.METHODS:We examined the influence of adiponectin defi ciency on colorectal carcinogenesis induced by the administration of azoxymethane(AOM)(7.5 mg/kg,in-traperitoneal injection once a week for 8 wk),by using adiponectin-knockout(KO) mice.RESULTS:At 53 wk after the fi rst AOM treatment,KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type(WT) mice,although the tumor incidence was not different between WT and KO mice.KO mice showed increased cell proliferation of colorec-tal tumor cells,which correlated with the expression levels of cyclooxygenase-2(COX-2) in the colorectal tumors.In addition,KO mice showed higher incidence and frequency of liver tumors after AOM treatment.Thirteen percent of WT mice developed liver tumors,and these WT mice had only a single tumor.In contrast,50% of KO mice developed liver tumors,and 58% of these KO mice had multiple tumors.CONCLUSION:Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice.This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

Tumor suppressor and hepatocellular carcinoma

A few signaling pathways are driving the growth of hepatocellular carcinoma.Each of these pathways possesses negative regulators.These enzymes,which normally suppress unchecked cell proliferation,are circumvented in the oncogenic process,either the overactivity of oncogenes is sufficient to annihilate the activity of tumor suppressors or tumor suppressors have been rendered ineffective.The loss of several key tumor suppressors has been described in hepatocellular carcinoma.Here,we systematically review the evidence implicating tumor suppressors in the development of hepatocellular carcinoma.

Methylation profiling of twenty four genes and the concordant methylation behaviours of nineteen genes that may contribute to hepatocellular carcinogenesis

To determine the possible role of the epigenetic mechanisms in carcinogenesis of the hepatocellular carcinoma, we methylation-profiled the promoter CpG islands of twenty four genes both in HCC tumors and the neighboring non-cancerous tissues of twenty eight patients using the methylation-specific PCR (MSP) method in conjunction with the DNA sequencing. In comparison with the normal liver tissues from the healthy donors, it was found that while remained unmethylated the ABL, CAV, EPO, GATA3, LKB1, NEP, NFL, NIS and p27^(KIP1) genes, varying extents of the HCC specific hypermethylation were found associated with the ABO, AR, CSPG2, cyclin al, DBCCR1, GALR2, IRF7, MGMT, MT1A, MYOD1, OCT6, p57^(KIP2), p73, WT1 genes, and demethylation with the MAGEA1 gene, respectively. Judged by whether the hypermethylated occurred in HCC more frequently than in their neighboring normal tissues, the hypermethylation status of the AR, DBCCR1, IRF7, OCT6, and p73 genes was considered as the event specific to the late stage, while that the rest that lacked such a distinguished contrast, as the event specific to the early stage of HCC carcinogenesis. Among all the clinical pathological parameters tested for the association with, the hypermethylation of the cyclin al gene was more prevalent in the non-cirrhosis group (P=0.021) while the hypermethylated p16^(INK4a) gene was more common in the cirrhosis group (P=0.017). The concordant methylation behaviors of nineteen genes, including the four previously studied and their association with cirrhosis has been evaluated by the best subgroup selection method. The data presented in this report would enable us to shape our understanding of the mechanisms for the HCC specific loss of the epigenetic stability of the genome, as well as the strategy of developing the novel robust methylation based diagnostic and prognostic tools.

A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.