Roles of Fibroblast Growth Factor-inducible 14 in Hepatocellular Carcinoma

The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma(HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were hereperformed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Mostof the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, withFn14High accounting for 54.6% (142/260) of all patients. The Pearson χ2 test indicated that Fn14 expression wasclosely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate andmultivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type,Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence(HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this moleculemay be a candidate biomarker for prognosis as well as a target for therapy.     

Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Most patients still present late in the course of the disease so that curative therapy is rarely possible. Strategies developed to improve the prognosis include primary prevention, directed at the underlying liver diseases, secondary prevention by cancer surveillance and early intervention, and more effective therapies. Only childhood vaccination against hepatitis B (HBV) infection has been clearly documented to reduce the incidence of HCC. Eradication of the hepatitis B and C viruses by interferon in noncirrhotic patients may reduce the incidence of HCC. Removal of iron by phlebotomy in noncirrhotic patients with genetic hemochromatosis will largely prevent HCC. Many physicians offer secondary prevention by surveillance and early intervention involving repeated abdominal ultrasound and serial serum α-fetoprotein estimations in order to identify early malignant lesions, but such strategies have yet to be proven to reduce mortality from HCC. Nonetheless, early detection would seem to offer a greater chance for application of potentially curative therapy. Different surveillance strategies may be necessary in different patient groups. For example, in chronic hepatitis C the increased risk of HCC seems to be confined to patients with established cirrhosis, whereas even noncirrhotic patients with HBV have a substantially increased risk of HCC. In high-risk patients, such as those with cirrhosis following chronic viral hepatitis, several factors can be identified which appear to confer additional risk. Examples are hepatocyte dysplasia found on biopsy, or non-neoplastic vascular nodules on computed tomography scanning. The management of such patients needs urgent resolution. Potentially curative treatment options include resection, liver transplantation, and alcohol injection or radiofrequency ablation. Resection in ideal candidates may provide up to 60% survival at 5 years. Liver transplantation may result in a 5-year survival of up to 70%. However, the shortage of organ donors means that tumor progression while on the waiting list will disqualify some patients, while others will die before an organ becomes available. Local ablation has been reported to be as effective as resection and is applicable to a larger proportion of patients. Of the palliative forms of therapy only chemoembolization has been shown to provide a significant improvement in life-span, although other forms of adjuvant and palliative therapy are under investigation.     

Predictive Value of Serum Insulin-like Growth Factor-1 in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver inthe world. Insulin-like growth factor-1 (IGF-1) levels reflect hepatic function and are inversely correlated withthe severity of background chronic liver disease. Objective: This study evaluated whether basal serum IGF-1levels can predict prognosis of HCC patients according to different risks of disease progression. Materials andMethods: A total of 89 patients with hepatocellular carcinoma (HCC) were recruited in 3 groups: Group I, 30HCC patients receiving sorafinib; Group II, 30 HCC patients with best supportive care; and Group III include29 patients undergoing transcatheter arterial chemoembolization (TACE). All patients were investigated forserum levels of AST, ALP, Bb, Cr, BUN, AFP and IGF-I. Results: Patients with disease control had significantlyhigher baseline IGF-1 levels 210 (185-232.5) ng/mL (p value<0.01) than did patients without disease control.Low basal IGF-1 levels were associated with advanced HCC, such as multiple tumors and advanced stage, andlow IGF-1 levels predicted shorter TTP and overall survival in patients treated with TACE. Conclusions: Thelevels of serum IGF-1, expressed as continuous values, may be helpful for accurately assessing hepatic functionand the prognostic stratification of patients with HCC.     

S100A14 Promotes the Growth and Metastasis of Hepatocellular Carcinoma

Background: S100A14 has recently been implicated in the progress of several types of cancers. This studyaimed to investigate the clinical significance and possible mechanisms of action of S100A14 in the invasion andmetastasis of hepatocellular carcinoma (HCC). Methods: S100A14 expression in HCC was detected at mRNA andprotein levels and its prognostic significance was assessed. Functional roles of S100A14 in HCC were investigatedusing MTT, BrdU, wound healing, transwell invasion assay and HCC metastatic mouse model. Results: S100A14was significantly elevated in HCC tissues, correlated with multiple tumor nodes, high Edmondson-Steiner gradeand vascular invasion. Multivariate Cox analysis showed that the S100A14 expression level was a significant andindependent prognostic factor for overall survival (OS) of HCC patients (hazard ratio=1.98, 95% confidenceinterval=1.14-3.46, P=0.013). S100A14 promoted cell proliferation, invasion and metastasis of HCC in vitro andin vivo. Conclusion: These results suggest S100A14 is a novel prognostic marker and therapeutic target for HCC.     

内皮生长因子G61A位点基因多态性与肝细胞癌易感性的Meta分析

肝细胞恶变和肿瘤进展的发病机制包括多种基因改变和分子信号通路调节等。其中,内皮生长因子(EGF)及受体信号通路的调节异常在肝细胞癌(HCC)的发生中具有重要作用。目前,国内外很多研究显示,EGF基因61A/G位点的功能多态性与人类多种恶性肿瘤相关。然而,关于EGF61A/G基因多态性与HCC易感性关系的各个研究样本量相对较小,且结果不尽     

Downregulated Expression of PTPN9 Contributes to Human Hepatocellular Carcinoma Growth and Progression

Human hepatocellular carcinoma (HCC) is one of the most common malignant cancers, whose molecular mechanisms is remains largely. PTPN9 has recently been reported to play a critical role in breast cancer development. However, the role of PTPN9 in human HCC remains elusive. The present study aimed at investigating the potential role of PTPN9 in HCC. Western blot and immunohistochemistry were used to examine the expression of PTPN9 protein in HCC and adjacent non-tumorous tissues in 45 patients. Furthermore, Cell Counting Kit-8, flow cytometry and RNA interference experiments were performed to analyze the role of PTPN9 in the regulation of HCC cell proliferation. We showed that the expression level of PTPN9 was significantly reduced in HCC, compared with adjacent non-tumorous tissues. PTPN9 expression was inversely associated with Tumor size (P?=?0.014), serum AFP level (P?=?0.004) and Ki-67 expression. Low expression of PTPN9 predicted poor survival in HCC patients. Moreover, PTPN9 interference assay that PTPN9 inhibited cell proliferation in HepG2 cells. Cell apoptosis assay revealed that, silencing of PTPN9 expression significantly reduced cell apoptosis, compared with control ShRNA treatment group. Our results suggested that PTPN9 expression was down-regulated in HCC tumor tissues, and reduced PTPN9 expression was associated with worsened overall survival in HCC patients. Depletion of PTPN9 inhibits the apoptosis and promotes the proliferation of HCC cells.     

Metformin Inhibits Growth of Hepatocellular Carcinoma Cells by Inducing Apoptosis Via Mitochondrion-mediated Pathway

Recently, population-based studies of type 2 diabetes patients have provided evidence that metformin treatment is associated with a reduced cancer incidence and mortality, but its mode of action remains unclear. Here we report effects of metformin on hepatocellular carcinoma (HCC) Hep-G2 cells and details of molecular mechanisms of metformin activity. Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway. Furthermore, we showed that metformin strongly attenuated colony formation and dramatically inhibited Hep-G2 tumor growth in vivo.In conclusion, our studies suggested that metformin might have potential as a cytotoxic drug in the prevention and treatment of HCC.     

Non-Viral Causes of Hepatocellular Carcinoma

Introduction

Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. The vast majority of cases occur in individuals with a chronic HBV or HCV infection. In addition, a number of metabolic diseases of the liver are associated with the development of HCC.

Pathophysiologic Mechanisms

The mechanisms responsible for the progression of the metabolic liver disease and HCC differ from those associated with viral liver disease.

Conclusions

The purpose of this report is to describe the mechanisms responsible for the disease progression and HCC in case of metabolic liver disease. A secondary goal is to identify the frequency of HCC development in the disorders described.     

肝细胞癌治疗方法的选择

肝细胞癌（ｈｅｐａｔｏｃｅｌｌｕｌａｒｃａｒｃｉｎｏｍａ,ＨＣＣ）是最常见的恶性肿瘤之一,预后较差。对ＨＣＣ采取的治疗方法很多,疗效不一。如何选择适宜的治疗方法？总结近５年来的国内外文献,综述如下。１肝部分切除术（ｈｅｐａｔｉｃｒｅｓｅｃｔｉｏｎ,ＨＲ）在我国ＨＣＣ被发现时,只有约１０．０％的患者适合手术切除,原因是多数病例在确诊时肿瘤已达Ⅲ期或Ⅳ期或合并严重的肝功能不全。肝癌的期别、肝功能储备、术式及手术前后是否采用综合治疗等因素,显著影响远期生存率。上海医科大学肝癌研究所报道ＨＲ后的１０年生…     

血清血管内皮生长因子在肝癌介入栓塞后的表达

目的探讨血清血管内皮生长因子(VEGF)在肝癌栓塞化疗(TACE)后的表达水平和临床意义。方法分析63例肝细胞肝癌患者的血管造影结果和VEGF血清表达水平,采用ELISA法检测40例TACE前后患者血清VEGF的变化。结果 43例肿瘤富血管患者血清VEGF水平高于20例肿瘤乏血管患者[(136.80±52.13)pg/mlvs(62.30±31.17)pg/ml,P<0.05];患者肝动脉栓塞治疗前后血清VEGF分别为(87.41±43.16)pg/ml和(128.42±43.12)pg/ml,P<0.05.其中有36例患者血清VEGF水平在肝动脉栓塞治疗后升高,第二次血管造影发现27例新生肿瘤血管的患者血清VEGF水平显著升高(179.13±66.27)pg/ml。血清VEGF浓度明显升高的患者介入治疗疗效较差。结论肝癌TACE后肿瘤细胞表达VEGF增强,血清VEGF是影响肝癌栓塞化疗效果的因素之一。     

血小板衍生生长因子-D在肝细胞肝癌中的表达及其临床意义

目的研究血小板衍生生长因子(PDGF) D在肝细胞肝癌(HCC)中的表达及其与临床病理指标的关系。方法用RT-PCR方法检测PDGF-A、B、C、D及其受体PDGFRα和PDGFRβ基因在40例肝癌组织及对应的30例癌旁组织和10例正常肝组织标本中mRNA的表达。结果HCC组织中PDGF-A、B、C、D及其受体PDGFRα和PDGFRβ阳性表达分别为37.5%(15/40)、70%(28/40)、52.5%(21/40)、92.5％(37/40)、22.5％(9/40)、42.5%(17/40);与其相对应的癌旁组织的阳性表达率分别为23.3％(7/30)、16.7%(5/30)、16.7%(5/30)、26.7%(8/30)、13.3%(4/30)、16.7%(5/30);而正常肝组织中未见表达。在HCC组织中PDGF家族的表达均显著高于癌旁组织和正常组织,三组比较差异有统计学意义(P＜0.01),且PDGF-D的阳性表达显著高于PDGFs其他亚型(P＜0.05)。在HCC、癌旁、正常肝脏组织中PDGF-D平均光密度值为0.5900±0.0364、0.3954±0.0654、0,三者比较差异有统计学意义(P＜0.01)。HCC组织中PDGF-D的阳性表达与肿瘤的分化程度、淋巴及转移有关（P＜0.05）;与年龄、性别、肿瘤大小、血清AFP的值及门静脉癌栓无关(P＞0.05)。结论PDGF家族中以PDGF-D表达率最高且与肿瘤的分化程度和转移相关,提示PDGF家族,尤其是PDGF-D在HCC的发生、发展和转移中可能发挥着重要的作用,可作为肝癌辅助诊断指标和治疗靶点。     

Elevated Levels of Plasma Transforming Growth Factor-β in Patients with Hepatocellular Carcinoma

We measured the plasma transforming growth factor-β (TGF-β) concentration in 14 patients with human hepatocellular carcinoma (HCC) and 9 age-matched normal subjects using growth inhibition assay of mink lung epithelial cells. The calculated plasma TGF-β concentration in the patients with HCC was 28.6 ± 27.9 ng/ml (mean± SE), showing significant elevation compared with that in 9 normal subjects (5.3 ± 3.3 ng/ml, P<0.01). In three cases, we could measure plasma TGF-β levels before and after their treatment for HCC. The plasma TGF-β levels decreased from 59.0 to 18.2 ng/ml after hepatic resection in one case, and from 24.0 to 10.7 ng/ml and from 12.4 to 3.4 ng/ml after transhepatic arterial embolization in the other two cases. These data indicate that plasma TGF-β level is elevated in patients with HCC, probably due to release from HCC tissues.     

肝细胞癌的基因治疗

肝细胞癌(HCC)是世界上一些地区最常见的恶性肿瘤之一,预后极差.肝细胞癌发生的分子机制核心是多种基因突变和遗传不稳定,这些情况大多数来自慢性肝脏病及相关的肝细胞再生及有丝分裂活性增强.     

Therapeutic Options in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is common in Africa as well as south eastern Asia, and is usually related to chronic hepatitis B virus infection although chronic hepatitis C virus infection and alcohol abuse also play a major role. Mass vaccination against the hepatitis B virus in neonates has been undertaken in Taiwan and South Africa with encouraging results. The treatment of choice for HCC is surgery, but radical resection is only feasible in a small percentage of patients because of the advanced nature of the disease and underlying liver cirrhosis. If surgical resection is not feasible, intra-arterial chemoembolization may reduce the size of tumors providing good palliation, and possibly render inoperable tumors operable. Locally ablative therapies including percutaneous ethanol injection, cryosurgery, microwave coagulation, and radiofrequency thermal ablation are useful in patients with limited disease, but are methods that are only feasible in highly specialized units. Liver transplantation, which is also only available in highly specialized centers, has unfortunately been disappointing. Unresectable HCC has a very poor prognosis, as the disease is highly refractory to most chemotherapy agents, possibly as a result of overexpression of the multidrug resistance gene, mdr1. Overall response rates of 10–15% have been reported with most chemotherapeutic agents, with doxorubicin probably being the most active agent. Other agents studied include fluorouracil as well as the newer oral fluoropyrimidines, etoposide, gemcitabine, anthracycline analogues including mitoxantrone, epirubicin, and pegylated liposomal doxorubicin, as well as cisplatin and the direct thymidylate synthase inhibitors raltitrexed and nolatrexed. Other agents including tamoxifen, tyrosine kinase inhibitors, thalidomide, interferons, and clofazimine have also been studied. Administration of viral vectors containing the p53 gene, or other tumor suppressor and suicide genes, is also a possible future therapy. Unfortunately as current approaches still remain unsatisfactory, especially in patients with advanced unresectable disease, newly diagnosed patients should, whenever available, be entered onto clinical studies with new agents which may result in better therapies for this highly refractory disease.