Extrahepatic recurrence after curative resection of hepatocellular cancer / 中华普通外科杂志

Objective To investigate the risk factors of extrahepatie recurrences after curative resection of primary hepatocellular carcinoma (HCC). Methods Clinicopathologic data of 238 curative resected cases of primary HCC were retrospectively reviewed for parameters affecting postoperative extrahepatic recurrences. Results During a median follow-up of 34 months (7 - 78 months), extrahepatic recurrences were observed in 32 out of 238 patients (13.4%). According to univariate analysis, the risk factors for extrahepatic recurrences were preoperative serum a-fetoprotein (AFP) level of > 1000 ng/ml,aspartate aminotransferase level of > 50 IU/L, presence of hepatic vein invasion, neighboring organ invasion, tumor satellites, and lack of tumor capsule formation. Preoperative serum AFP levels of > 1000 ng/ml, hepatic vein invasion, neighboring organ invasion proved to be independent risk factors by multivariate analysis. Conclusions Extrahepatic recurrences after curative resection of HCC was found to be related to preoperative serum AFP level of > 1000 ng/ml, hepatic vein invasion, and neighboring organ invasion.

Effects of troglitazone on the proliferation and differentiation of HepG2 cells / 中华消化外科杂志

Objective To examine the effects of a peroxisome proliferator-activated receptor γ ligand troglitazone on the proliferation and differentiation of HepG2 cells. Methods After the pretreatment of HepG2 cells with troglitazone, MTT and flow cytometry were used to analyze the proliferation and cell cycle of HepG2 cells, respectively. Immunocytochemistry, bromocresol green dye-binding method and chemiluminessence immunosorbent assay was used to determine E-cadherin, albumin and AFP, respectively. The expression of cyclin D1 and c-myc protein were detected by Western blot. Results Troglitazone inhibited the proliferation of HepG2 cells in a concentration-dependent manner and arrested HepG2 ceils at the G0>/G1> phase. After pretreated with troglitazone, HepG2 cells showed E-cadherin expression, a decreased expression of cyclin D1 and c-myc protein, a reduction of AFP level and a dramatic increase of albumin level. Conclusions Troglitazone inhibits proliferation and induces differentiation of HepG2 cells, the mechanism of which might be attributable to the down-regulation of cyclin D1 and c-myc expression.

The correlation between hepatitis virus infection and p53 expression in cholangiocarcinoma tissues / 中华普通外科杂志

Objective To assess hepatitis B virus(HBV)and hepatitis C virus(HCV)infections in different anatomic location of cholangiocarcinoma(CC)and relationship with abnormal p53 expression.Methods A total of 411 CC samples including intrahepatic cholangiocarcinoma(ICC 312 cases);perihilar cholangiocarcinoma(PHC,73 cases)and distal cholangiocarcinoma(DC,26 cases)underwent serologic test for HBsAg and anti-HCV using microparticle enzyme immunoassay.Abnormal p53 expression was detected in formalin-fixed.paraffin-embedded CC tissues by immunohistochemistry.Results Seropositivity for HBsAg and anti-HCV were found in 48.4%(151/312)and 2.9%(9/312)of ICC cases,and in 10.9%(8/73)and zero of PHC,and in 7.7%(2/26)and zero of DC,respectively.Abnormal p53 expression was detected in 30.1%(94/312)of ICC cases.23.3%(17/73)of PHC cases and 19.2%(5/26)of DC cases.There was no correlation between seropositivity of HBsAg and anti-HCV and p53 overexpression among three groups of CC. Conclusions HBV but not HCV infection may be associated with the development of ICC.p53 abnormality may not play a significant role in HBV-associated carcinogenesis of ICC.

Hypoxia augments the killing effect of herpes simplex virus thymidine kinase gene expression actuated by the promoter of the vascular endothelial growth factor gene on human hepatocellular tumor cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the killing effect of herpes simplex virus thymidine kinase gene expression actuated by the promoter of the vascular endothelial growth factor gene on human hepatocellular tumor cells under hypoxic condition.</p><p><b>METHODS</b>Recombinant adenoviral vectors, AdVEGF-tk and AdVEGF-GFP, were constructed with HSV-tk or GFP under the control of VEGF promoter through AdEasy system. Then GFP expression in hepatoma cell line HepG2 and normal liver cell line L02 transfected with AdVEGF-GFP were observed under fluorescence microscope, and the sensitivity to GCV of the AdVEGF-tk-transfected cells under normoxia or hypoxia condition were monitored by MTT method.</p><p><b>RESULTS</b>GFP expression actuated by VEGF promoter was detected in sporadic L02 cells, but in almost all HepG2 cells after transfected with AdVEGF-GFP. With GCV at 10 micro g/ml and MOI at 100, L02 cells were insensitive to GCV under oxic condition, but more than 70% L02 cells were killed under hypoxic condition. Moreover, HepG2 cells infected with AdVEGF-tk showed the increased GCV sensitivity under hypoxia (over 80% killed) as compared with normoxia (over 60% killed) conditions.</p><p><b>CONCLUSION</b>Hypoxia enhances the GCV sensitivity of human hepatocellular tumor cells infected with recombinant AdVEGF-tk under the control of VEGF promoter.</p>

Correlation between midkine protein overexpression and intrahepatic metastasis in hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation between midkine (MK) protein expression with local infiltration and metastasis in human hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Immunohistochemical and Western Blot analysis for MK were performed on samples of tumor tissue and the paratumor tissue from HCC and benign liver tumors.</p><p><b>RESULTS</b>The overexpression of MK protein determined by immunohistochemical analysis was similar to that by Western Blot analysis. No specific positivity was detected in either benign liver tumor tissue or normal liver tissue, but most of HCC tissue showed a positive reaction to MK immunostain. No correlation between MK expression and other clinicopathological features in MK negative or positive HCC cases was found. Yet, the overexpression rate of MK protein in HCC with intra-hepatic metastasis was significantly higher than that in HCC without intra-hepatic metastasis.</p><p><b>CONCLUSION</b>In human hepatocellular carcinoma, MK overexpressed at protein level may very well be closely related to local infiltration and metastasis.</p>

Study on asialoglycoprotein receptor-mediated liver targeting:current progress / 第二军医大学学报

Asialoglycoprotein receptor(ASGPR),also called galactose receptor,is predominantly expressed on the sinusoidal surface of mammalian hepatocytes and is involved in many physiological functions.For many years ASGPR has been applied for targeting hepatocytes in drug and gene delivery and for functional mapping of the liver,and considerable progress has been made.ASGPR-mediated liver-targeted drug delivery mainly involved anti-tumor drugs and cholesterol-lowering drugs,etc.Liver-targeted gene delivery was often seen in antisense drugs.The research of hepatic imaging mainly involved the evaluation of liver function and identification between hepatocellular carcinoma and hepatic metastasis of tumors.In addition,researchers have also extended its applications to some new fields,such as three-dimension culture of hepatocytes,hepatocytes screening,and hepatocytes transplantation.New achievements in studies of ASGPR-mediated liver targeting are reviewed in this article.

Oxidative stress and cell signal transduction / 第二军医大学学报

Oxidative stress is a major cause of fatty liver,atherosclerosis,cancer,organ damage following ischemia/reperfusion,etc.In recent years,significant improvements have been achieved in studies on signaling pathways involved in oxidative stress,which provide a basis for the drug and gene therapy.This article reviews the major redox-related signaling molecules and pathways,including transcription factors,growth factor signaling,tyrosine kinases and serine/threonine kinases.

Therapeutic efficacy of adenovirus-mediated gene transfer of thymidine kinase coded with vascular endothelial growth factor promoter on murine experimental hepatocellular carcinoma / 中国普通外科杂志

0.05). The mean growth values in AdCMV-tk/GCV- and AdVEGF-tk/GCV-treated tumors were significantly lower than those in untreated tumors and AdVEGF-tk/saline-untreated tumors( P

Anticancer effects of PPAR? agonists:recent progress / 第二军医大学学报

Peroxisome proliferator-activated receptor(PPAR) belongs to the superfamily of nuclear hormone receptor.Three PPAR subtypes have been identified to date(PPAR?,PPAR? and PPAR?)and the relationship between PPAR? and tumor has drawn great attention.Current data showed that PPAR? agonists exert their antineoplastic effect through inhibiting cell growth and angiogenesis,inducing cell apoptosis and differentiation,and reducing tumor invasive ability.PPAR? agonists may be a promising tool for cancer chemotherapy.

Relationship between fatty acid synthase and human epidermal growth factor receptor-2 in tumor cells / 第二军医大学学报

Tumor cells have different physiological and biochemical features as compared to normal cells;abnormal expressi of certain genes is also found in tumor cells.Over-expression of genes provide targets for targeted-administration of drugs,which can avoid damage to normal cells during treatment of tumors.Fatty acid synthase(FAS)and human epidermal growth factor receptor-2(HER2)are both over-expressed in some tumor cells.Herceptin,an HER2-targeted agent,has been used to treat HER2-positive breast cancer patients worldwide and has obtained satisfactory outcome.Cerulomycin,an agent-targeting FAS,is now in FDA clinical trial.Recent researches have shown that FAS and HER2 are simultaneously over-expressed in some tumors,such as breast cancer cells and ovarian cancer cells;and there is a connection between their signal pathways and a synergistic effect between them.This paper reviews the relationship between FAS and HER2 in tumor cells.

Expression and localization of midkine in hepatocellular carcinoma / 中国普通外科杂志

ObjectiveTo investigate the expression and localization of midkine (MK) in human hepatocellular carcinoma. MethodsIn situ hybridization and immunohistochemical analysis for MK were performed on samples of both tumor tissues and paratumor tissues from HCC and benign liver tumors. ResultsThe distribution and localization of the MK transcripts′ signals determined by in situ hybridization were similar to those obtained by immunohistochemical analysis. Most HCC tissues showed enhanced positive reaction within cytoplasm to both MK probe and MK immunostaining. There was no significant difference in clinicopathological parameters between MK negative and positive cases of HCC. ConclusionsHuman hepatocellular carcinoma overexpresses MK at the mRNA and protein level.

Oncogenes in the regulation of tumor angiogenesis / 中国病理生理杂志

Oncogene activation and tumor suppressor gene loss are well known as events that are responsible for the dramatic cell autonomous deregulation of growth that characterizes all malignant cells. Data accumulating more recently indicate that these same genes are also responsible for the development of a second essential characteristic of all malignant cells, the ability to induce angiogenesis on which their progressive growth in vivo depends. Oncogene activation appears to make distinctly different contributions to the angiogenic phenotype of developing tumors. Cells in which an oncogene is activated become more an- giogenic usually because they increase their secretion of inducer of angiogenesis. Inducer enhancement seems to be essential if a normal cell is to develope into a tumor cell able to grow and metastasize in vivo.

Alpha-fetoprotein Reactive to Pisum Sativum Agglutinin in Liver Tumor Tissues and Sera from Patients with Primary Liver Cancer / 第二军医大学学报

Alpha-fetoprotein reactive to pisum sativum agglutinin (AFP-R-P) in liver tumor tissues, surrounding noncancerous tissues and peripheral blood from 25 cases of primary liver cancer were measured. Their medium and standard deviation were 41 ?26%, 30?27% and 36?25%, respectively. AFP-R-P levels were lower in the tumors with a diameter of less than 3cm, intact capsule, no invasion of surrounding liver tissues and no tumor thrombus. The patients with lower AFP-R-P levels had a longer survival. The results indicate that AFP-R-P is secreted mainly by tumor cells possessing more malignant behaviour, diffused directly in surrounding liver tissues and entered into peripheral blood, resulting in elevated serum AFP-R-P.

Relationship between Fucosylated ?-fetoprotein Levels and ?-L-fucosidase Activities in Sera from Patients with Hepatocellular Carcinoma / 第二军医大学学报

The increased binding of serum a-fetoprotein (AFP) from patients with hepatocellular carcinoma (HCC) to fucose-recognizing lectins has been reported. In order to study the enzymatic basis of this alteration, the serum activities of a-L-fucosidase (AFU) and fucosylated AFP (F-AFP) were determined in serum samples from 90 patients with HCC. Serum F-AFP levels were not related with serum AFU activities in HCC patients. When HCC patients grouped according to AFU activities were analyzed, the mean F-AFP level in 47 patients with a AFU activity below 550 nmol. ml-1. h-1 was 40%?23%, while the corresponding value for 43 patients with a AFU activity above 550 nmol . ml-1. h-1 was 45%?22%. No statistical significance was found between these values. The results indicate that changes in sugar chain structure of AFP in HCC patients do not result from increased or decreased activities of serum AFU.

Isolation and detection of circulating tumor cells:recent progress / 第二军医大学学报

Disseminated malignancy is the main cause of cancer-related death.The spontaneous circulation of tumor cells is responsible for distant metastasis;therefore it is of potential importance to specifically and sensitively detect the circulating tumor cells,which not only allows for more accurate prediction of cancer prognosis,but also helps to tailor individualized anticancer treatment.This paper reviews the enrichment,detection and analyzing methods of circulating tumor cells.

Detection and clinical implication of minimal residual cancer cells in patients with solid tumors / 第二军医大学学报

After surgical removal of a primary tumor the minimal residual cancer cells (MRCC) and metastases derived thereof are the actual targets for all theraputic approaches. Due to the great sensitivity and PCR-based detection systems, the molecular characterization of MRCC can provide information about their metastatic potential, availability of drug targets, drug sensitivity and development of therapy resistance, which will close the analytical gap between primary disease and the detection of metastases by conventional methods such as imaging procedures, and this will help therapy selection, monitoring of the treatment effects and predicting of the prognosis. Patients will benefit from a individualized therapy in the end.

DIAGNOSTIC VALUES OF ASSAY FOR ABNORMAL PROTHROMBIN IN PATIENTS WITH PRIMARY HEPATOCELLULAR CARCINOMA / 第二军医大学学报

In this study, we determined plasma abnormal prothrombin concentrations in 98 patients with histologically-proved primary hepatoceliular carcinoma (HCC) and 181 patients with other diseases using a radio-rocket electrophoresis autography. Out of 98 patients with HCC, 68 had abnormal prothrombin levels above or equal to 250 ?g/L and the positively was 69.4%, which was much higher than that in other groups. Abnormal prothrombin levels correlated poorly with those of alpha-fetoprotein (AFP)(r = 0.317), The positiveties of abnormal prothrombin level in HCC with low AFP level and with AFP negative were 63.8% and 65.5%. respectively. When used in combination, both tests could identify 84.7% of patients with HCC and 84.2% of patients with small HCC, respectively. The results show that the assay for plasma abnormal prothrombin may be useful in diagnosing low AFP-producing or AFP negative HCC, and also in discriminating HCC from chronic liver diseases and benign tumors of liver.