Normal Hepatic Tissue Research Articles

Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis.

Polycystic livers are seen in the rare inherited disorder isolated polycystic liver disease (PCLD) and are recognized as the most common extrarenal manifestation in autosomal dominant polycystic kidney disease. Hepatic cystogenesis is characterized by progressive proliferation of cholangiocytes, ultimately causing hepatomegaly. Genetically, polycystic liver disease is a heterogeneous disorder with incomplete penetrance and caused by mutations in PRKCSH, SEC63, PKD1, or PKD2. Genome-wide SNP typing and Sanger sequencing revealed no pathogenic variants in hitherto genes in an extended PCLD family. We performed whole-exome sequencing of DNA samples from two members. A heterozygous variant c.3562C > T located at a highly conserved amino acid position (p.R1188W) in the low density lipoprotein receptor-related protein 5 (LRP5) gene segregated with the disease (logarithm of odds score, 4.62) but was not observed in more than 1,000 unaffected individuals. Screening of LRP5 in a PCLD cohort identified three additional mutations in three unrelated families with polycystic livers (p.V454M, p.R1529S, and p.D1551N), again all undetected in controls. All variants were predicted to be damaging with profound structural effects on LRP5 protein domains. Liver cyst tissue and normal hepatic tissue samples from patients and controls showed abundant LRP5 expression by immunohistochemistry. Functional activity analyses indicated that mutant LRP5 led to reduced wingless signal activation. In conclusion, we demonstrate that germ-line LRP5 missense mutations are associated with hepatic cystogenesis. The findings presented in this study link the pathophysiology of PCLD to deregulation of the canonical wingless signaling pathway.

Suppression of CUGBP1 inhibits growth of hepatocellular carcinoma cells

The multifunctional RNA-binding protein, CUGBP1, regulates splicing, stability and translation of mRNAs. Previous studies have shown that CUGBP1 is expressed at high levels in the liver, although its role in hepatocellular carcinoma is unknown. Our aim was to determine if CUGBP1 could regulate hepatocellular carcinoma growth. Expression levels of CUGBP1 were analyzed in 70 hepatic carcinoma and 20 normal hepatic tissue samples by immunohistochemistry (IHC). Using lentivirus-mediated short hairpin RNA (shRNA), CUGBP1 expression in human hepatocellular carcinoma HepG2 cells was knocked-down. The effect of CUGBP1 on hepatic cancer cell growth was investigated. CUGBP1 was expressed in 85.7% hepatocellular carcinoma specimens compared with 50% in normal liver specimens. CUGBP1 silencing remarkably decreased the proliferation of HepG2 cells, as determined by MTT assay. Flow cytometry analysis showed that knock-down of CUGBP1 led to G0/G1 phase cell cycle arrest, accompanied by sub-G1 accumulation. Moreover, depletion of CUGBP1 resulted in downregulation of cyclin B1 and upregulation of cyclin D1. These results suggest that CUGBP1 is essential for the growth of hepatocellular carcinoma cells. Knockdown of CUGBP1 might be a potential therapeutic approach for human hepatocellular carcinoma.

Reexpression of Let-7g MicroRNA Inhibits the Proliferation and Migration via K-Ras/HMGA2/Snail Axis in Hepatocellular Carcinoma

Let-7 family microRNAs have been reported to be downregulated in human hepatocellular carcinoma in comparison with normal hepatic tissues. Among them, let-7g was identified as the lowest expression using real-time RT-PCR. However, the mechanism by which let-7g works in hepatocellular carcinoma remains unknown. Here, in our present study, we have had let-7g reexpressed in vitro in hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The proliferation after reexpression of let-7g was assayed using MTT method; the migration and invasion after restoration were detected by wound-healing and Transwell assay, respectively. We found using Western-blotting that let-7g can regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or not reexpression of let-7g could have potential therapeutic ability. In vivo, to observe the association with let-7g expression and overall prognosis, 40 paired cases of hepatocellular carcinoma were analyzed using in situ hybridization (ISH). It was found that reexpression of let-7g can inhibit the proliferation, migration, and invasion significantly, and that low expression of let-7g was significantly associated with poorer overall survival. Taken together, let-7g could be used as a promising therapeutic agent in vivo in the treatment of hepatocellular carcinoma at the earlier stage.

Monoclonal Antibody Preparation and Expression Profile Analysis of a Novel Hepatoma Associated Gene

Hepatoma associated gene (HTA), a gene screened and cloned by our previous research, was specifically expressed in certain kinds of tumors and had a cancer-promoting role in hepatocellular carcinoma (HCC). To further elucidate the mechanism of HTA in hepatoma carcinogenesis and its potential role as a cancer biomarker, refolded HTA protein (HTA) was obtained by prokaryotic recombinant expression system and immobilized metal affinity chromatography. Then anti-HTA monoclonal antibody (mAb) was produced by hybridoma technique. Using the high titer anti-HTA mAb with high specificity obtained, the expression profile of HTA was analysed by immunohistochemistry staining. It showed that HTA expressed specifically in some kinds of tumors, and didn't express in almost any of the normal tissues. The positive expression rate and expression quantity of HTA was significantly higher in HCC tissues than in hepatic cirrhosis tissues, hepatic fibrosis tissues and normal hepatic tissues. The expression of HTA was positively correlated with hepatoma carcinogenic process.

Musashi2 predicts poor prognosis and invasion in hepatocellular carcinoma by driving epithelial–mesenchymal transition

The high incidence of recurrence and the poor prognosis of hepatocellular carcinoma (HCC) necessitate the discovery of new predictive markers of HCC invasion and prognosis. In this study, we evaluated the expression pattern of two members of a novel oncogene family, Musashi1 (MSI1) and Musashi2 (MSI2) in 40 normal hepatic tissue specimens, 149 HCC specimens and their adjacent non-tumourous tissues. We observed that MSI1 and MSI2 were significantly up-regulated in HCC tissues. High expression levels of MSI1 and MSI2 were detectable in 37.6% (56/149) and 49.0% (73/149) of the HCC specimens, respectively, but were rarely detected in adjacent non-tumourous tissues and were never detected in normal hepatic tissue specimens. Nevertheless, only high expression of MSI2 correlated with poor prognosis. In addition, MSI2 up-regulation correlated with clinicopathological parameters representative of highly invasive HCC. Further study indicated that MSI2 might enhance invasion of HCC by inducing epithelial–mesenchymal transition (EMT). Knockdown of MSI2 significantly decreased the invasion of HCC cells and changed the expression pattern of EMT markers. Moreover, immunohistochemistry assays of 149 HCC tissue specimens further confirmed this correlation. Taken together, the results of our study demonstrated that MSI2 correlates with EMT and has the potential to be a new predictive biomarker of HCC prognosis and invasion to help guide diagnosis and treatment of post-operative HCC patients.

Effect of hepatitis C virus infection on erythropoiesis in patients on hemodialysis

BackgroundErythropoietin is a hormone that regulates erythropoiesis and is mainly produced by the kidneys. Several animal studies as well as a few case reports and case series have demonstrated that regenerating hepatic tissue can produce more erythropoietin than normal hepatic tissue. The purpose of the study was to examine the difference in hemoglobin and hematocrit levels as well as epoetin dosage in patients on hemodialysis with and without hepatitis C (HCV).MethodsA retrospective chart review was performed. Seventy-six patients were included in the study (19 with HCV and 57 without HCV) at a ratio of 1:3. Exclusion criteria were a history of gastrointestinal bleeding or blood transfusion over the previous six months, polycystic kidney disease, and pregnancy. Variables examined included gender, age, duration of hemodialysis, hemoglobin, hematocrit, epoetin dose, aspartate transaminase, and ferritin levels over a three-month period.ResultsThe patients were divided into two groups. The first consisted of patients with HCV on hemodialysis and the second of patients on hemodialysis without HCV. Mean hemoglobin was 12.6 ± 1.2 g/dL for the HCV-positive group and 11.9 ± 1.1 g/dL for the HCV-negative group. The difference was statistically significant (P = 0.03). Mean hematocrit was higher in the HCV-positive group, but was not significantly different at 39.08% ± 4.06% versus 37.43% ± 3.4% in the HCV-negative group (t-test, P = 0.11). Further, the HCV-positive group required less epoetin, but this was not significantly different from that required in the HCV-negative group at 6258 ± 5208 IU versus 7596 ± 7056 IU, respectively (t-test, P = 0.38).ConclusionIn our study, patients with HCV infection were found to have higher hemoglobin and hematocrit levels and lower epoetin requirements than those without HCV. Although the findings were not statistically significant, the computed values between these two groups of patients did follow a general trend. Further investigation with more patients, a longer duration of follow-up, and incorporation of additional medical variables is needed to clarify the role of HCV on erythropoiesis in hemodialysis patients.

Trans-resveratrol loaded chitosan nanoparticles modified with biotin and avidin to target hepatic carcinoma

Conventional liver targeted system focuses on delivering drugs to liver, bringing toxicity on hepatic normal tissues. The purpose of this study is to construct a new system capable of specially targeting to hepatic carcinoma instead of the whole liver. Based on the fact that nanoparticles (NPs) bound with either biotin or avidin tend to accumulate in tumors and avidin-attached reagents were quickly eliminated from blood circulation and assembled in liver, trans-resveratrol loaded chitosan nanoparticles (CS-NPs), CS-NPs with the surface modified either by biotin (B-CS-NPs) or by both biotin and avidin (A-B-CS-NPs) were prepared and their physiochemical properties were investigated. The in vitro release profiles of the three NPs all conformed to bioexponential equation. Pharmacokinetic experiment indicated that A-B-CS-NPs rapidly assembled in liver after injection, with the highest liver targeting index of 2.70, while the modification of biotin attenuated the liver targeting ability of NPs. Inhibitory study on HepG2 cells declared that compared to trans-resveratrol solution and CS-NPs, both B-CS-NPs and A-B-CS-NPs significantly improved the anticancer activity. When incubated with HepG2 cells at high concentration for longer time, A-B-CS-NPs exhibited superior cytotoxicity than B-CS-NPs. This study exclaims that A-B-CS-NPs may be a potent drug delivery vector specially targeting to hepatic carcinoma.

Cirrhosis classification based on MRI with duplicative-feature support vector machine (DFSVM)

Magnetic resonance imaging (MRI) is a sensitive diagnostic method in improving the diagnostic capacity for hepatic cirrhosis and determining the accurate characterization of hepatic cirrhosis. But hepatic MRI has some shortcomings in detection and classification hepatic cirrhosis in clinical, especially using non-enhanced MRI for diagnosing early hepatic cirrhosis. And computer-aided diagnostic (CAD) system, including quantitative description of lesion and automatically classification, can provide radiologists or physicians an alternative second opinion to efficiently apply the abundant information of the hepatic MRI. However, it is expected to character comprehensively the lesion and guarantee high classification rate of CAD system. In this paper, a new CAD system for hepatic cirrhosis detection and classification from normal hepatic tissue non-enhanced MRI is presented. According to prior approach, six texture features with different properties based on gray level difference method are extracted from regions of interest (ROI). Then duplicative-feature support vector machine (DFSVM) is proposed for feature selection and classification: Firstly, the search process of DFSVM imitates diagnosis of doctors: doctor will take a more feature for consideration until the final diagnoses regardless of whether the feature is used in advance. So our algorithm is consistent with the process of clinical diagnosis. Secondly, the impact of the most valuable features will be well strengthened and then the high prediction performance can be got. Experimental results also illustrate the satisfying classification rate. Performance of extracted features and normalization are studied. And it is also compared with typical classifier ANN.

AhR expression is increased in hepatocellular carcinoma

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor implicated in multiple cellular processes and its expression has been shown to play a critical role in tumorigenesis. However, the role of AhR in tumorigenesis of hepatocellular carcinoma remains unclear. In the current study, we investigated the role of AhR in hepatocellular carcinoma tumorigenesis and progression by (a) measuring the expression levels of AhR in liver lesions and (b) assessing the correlation between AhR expression and clinicopathologic parameters. The tissue microarray used in this study contained hepatocellular carcinoma tissues (n = 94), cancer adjacent normal hepatic tissues (n = 5) and normal hepatic tissues (n = 5), which were immunohistochemically assessed for AhR expression. Significantly stronger AhR staining was observed for hepatocellular carcinoma tissues than for cancer adjacent normal hepatic tissues (P = 0.003) and normal hepatic tissues (P = 0.004). In addition, AhR expression was associated with T stage (P = 0.03). The results from this study suggest that an increase in AhR expression is associated with hepatocellular carcinoma progression and may have a potential role in the treatment of hepatocellular carcinoma.

8:08 AM Abstract No. 60 - Fusion MAA-sulfur colloid spect imaging for Yttrium-90 radioembolization: towards customized physiology-based dose planning

Purpose Yttrium-90 (90Y) radioembolization dose planning requires balancing caution against toxicity with aggressiveness for efficacy, but each is impossible to predict based solely on morphologic imaging. We investigate the use of fusion MAA-sulfur colloid SPECT imaging to provide physiologic information relevant to dose calculation and outcomes. Materials and Methods A dual SPECT protocol was used with IA injection of technetium-99m (99mTc)-MAA (1 mCi) as a predictor of subsequent 90Y distribution, followed by IV 99mTc-sulfur colloid (5 mCi) as a biomarker for normal hepatic tissue. The SPECT data were co-registered and fused. A voxel based method was used to predict the 90Y radiation absorbed dose to functional hepatic tissue by calculation of 99mTc-MAA activity in voxels with 99mTc-sulfur colloid uptake. Similarly, the absorbed dose to tumor was predicted by calculation of 99mTc-MAA activity in voxels without 99mTc-sulfur colloid. Response (mRECIST) was recorded at 3 months, laboratory data were collected at 2, 4 and 8 weeks, and patients were followed until death. Retrospective SPECT based dosimetry was correlated with parameters of toxicity and efficacy and compared with standard parameters of dosimetry, administered activity, and whole liver absorbed dose. Results A total of 56 patients were included (32 M, 24 F; median age 62; 27 HCC, 29 CRC, 32 resin, 24 glass microspheres, median activity 2.02 GBq, median whole liver dose 70 Gray). Toxicity parameters (serum bilirubin, AST, ALT, albumin, hemoglobin, and platelets) correlated significantly with SPECT-based functional liver absorbed dose (median 38 Gy, p Conclusion Fusion MAA-Sulfur colloid SPECT is useful to predict tumor and functional liver absorbed dose, which correlate with efficacy and toxicity, and may be used in the future to develop an individualized physiology-based dose-planning method.

Values of spectral CT imaging in differential diagnosis of hepatocellular carcinoma and focal nodular hyperplasia

Objective To explore the application value of spectral CT multi-parameter imaging in the differential diagnosis of hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH). Methods Forty-eight patients with hepatic lesions underwent gemstone spectral imaging (GSI) scans,including 32 HCC and 16 FNH,to obtain spectral serial images for the arterial phase and portal venous phase (PVP).The spectral parameters of lesions,normal hepatic tissue and the aorta were measured.Then,the lesion-liver contrast-to-noise ratio (CNR) in the different energy levels,normalized iodine concentration (NIC),the lesion-normal parenchyma iodine concentration ratio (LNR) and iodine concentration difference (ICD) between the arterial phase and the portal venous phase were calculated.The above measurement results were analyzed with two samples t test and ROC curve. Results The CNR of HCC and FNH in the different energy levels showed a certain regularity.In general,with the single photon energy increased,the CNR decreased except for some energy points.For HCC and FNH,the optimal CNR were 3.59±2.13 and 8.29±2.65,respectively,during the arterial phase and 1.80±0.42 and 1.06±0.34,respectively,during the portal venous phase.The NIC were 0.25±0.08 and 0.42±0.22,respectively,during the arterial phase and 0.52±0.14 and 0.86±0.18,respectively,during the portal venous phase.The LNR were 2.97±0.50 and 6.15±0.97,respectively,during the arterial phase and 0.99±0.19 and 1.22±0.26,respectively, during the portal venous phase.The ICD were (0.35±0.14) and (1.17±0.28) g/L,respectively.The NIC,LNR and ICD for HCC were less than FNH during the arterial phase and the portal venous phase.There were significant differences in NIC (t=-3.196,the arterial phase;t=-6.518,the portal venous phase),LNR (t=-12.911,the arterial phase; t=-3.260,the portal venous phase),and ICD (t=-2.754) between HCC and FNH (P<0.05).LNR in the arterial phase had the highest sensitivity and specificity of 100% and 100% in differentiating HCC from FNH. Conclusion The use of spectral CT with the quantitative analysis of iodine concentration might be helpful for increasing the efficiency of the detection and accuracy of diagnosis of HCC and FNH. Key words: Liver neoplasms; Tomography,X-ray computed; Diagnosis,differential

GRK6 expression in patients with hepatocellular carcinoma

ObjectiveTo investigate the expression and potential roles of G protein-coupled receptor kinase 6 (GRK6) in hepatocellular carcinoma (HCC) patients. MethodsImmunohistochemistry and Western blot was performed to determine GRK6 expression in 73 HCC samples. And the correlation with clinicopathological features was also analyzed. ResultsGRK6 expression was significantly higher in HCC than that in normal hepatic tissue. GRK6 was positively correlated with proliferation marker Ki-67, clinical stage, metastasis and survival time. ConclusionsOur results suggested that GRK6 overexpression plays an important role in HCC. Monitoring the expression of GRK6 maybe helpful in early diagnosis and prognosis of HCC.

Methylation of multiple genes in hepatitis C virus associated hepatocellular carcinoma

We studied promoter methylation (PM) of 11 genes in Peripheral Blood Lymphocytes (PBLs) and tissues of hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC) and chronic hepatitis (CH) Egyptian patients. The present study included 31 HCC with their ANT, 38 CH and 13 normal hepatic tissue (NHT) samples. In all groups, PM of APC, FHIT, p15, p73, p14, p16, DAPK1, CDH1, RARβ, RASSF1A, O6MGMT was assessed by methylation-specific PCR (MSP). APC and O6-MGMT protein expression was assessed by immunohistochemistry (IHC) in the studied HCC and CH (20 samples each) as well as in a different HCC and CH set for confirmation of MSP results. PM was associated with progression from CH to HCC. Most genes showed high methylation frequency (MF) and the methylation index (MI) increased with disease progression. MF of p14, p73, RASSF1A, CDH1 and O6MGMT was significantly higher in HCC and their ANT. MF of APC was higher in CH. We reported high concordance between MF in HCC and their ANT, MF in PBL and CH tissues as well as between PM and protein expression of APC and O6MGMT. A panel of 4 genes (APC, p73, p14, O6MGMT) classifies the cases independently into HCC and CH with high accuracy (89.9%), sensitivity (83.9%) and specificity (94.7%). HCV infection may contribute to hepatocarcinogenesis through enhancing PM of multiple genes. PM of APC occurs early in the cascade while PM of p14, p73, RASSF1A, RARB, CDH1 and O6MGMT are late changes. A panel of APC, p73, p14, O6-MGMT could be used in monitoring CH patients for early detection of HCC. Also, we found that, the methylation status is not significantly affected by whether the tissue was from the liver or PBL, indicating the possibility of use PBL as indicator to genetic profile instead of liver tissue regardless the stage of disease.

Expression and Clinical Significance of Livin Protein in Hepatocellular Carcinoma

In this study, the two-step PV method of immunohistochemistry was used to determine livin protein expression in HCC tissues, pericarcinoma tissues, hepatitis/hepatic cirrhosis tissues, and normal hepatic tissues, and livin protein expression was detected in the blood plasma of patients with HCC before and after surgery, subjects with hepatic cirrhosis and hepatitis, and healthy blood donors using ELISA. Livin protein expression was significantly higher in HCC tissues than that in normal hepatic tissues and hepatitis/hepatic cirrhosis tissues, with no significant difference between HCC tissues and pericarcinoma tissues. The HCC patients with positive livin protein expression had a significantly higher survival rate than those with negative livin protein expression. Livin protein expression was significantly higher in the blood plasma of patients with HCC before and after surgery and in patients with hepatic cirrhosis and hepatitis than that in healthy blood donors, whereas livin protein expression in the blood plasma of patients with HCC was not significantly different from that of patients with hepatic cirrhosis and hepatitis. Livin protein expression in HCC tissues did not correlate with that in the blood plasma of the same HCC patients. Livin protein expression may be a potential, effective indicator for assessing prognosis in patients with HCC.

Preliminary Study on Hepatocyte-Targeted Phosphorus-31 MRS Using ATP-Loaded Galactosylated Chitosan Oligosaccharide Nanoparticles

Background. The clinical applications of hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) remain to be difficult because the changes of phosphates between normal hepatic tissues and pathological tissues are not so obvious, and furthermore, up to now there is few literature on hepatocyte-targeted 31P MRS. Materials and Methods. The ATP-loaded Gal-CSO (Gal-CSO/ATP) nanoparticles were prepared and the special cellular uptake of them as evaluated by using HepG-2 tumor cells and A549 tumor cells, respectively. Two kinds of cells were incubated with the nanoparticles suspension, respectively. Then were prepared the cell samples and the enhancement efficiency of ATP peaks detected by 31P MRS was evaluated. Results. The cellular uptake rate of Gal-CSO/ATP nanoparticles in HepG-2 cells was higher than that in A549 cells. Furthermore, the enlarged ATP peaks of Gal-CSO/ATP nanoparticles in HepG-2 cells were higher than those in A549 cells in vitro detected by 31P MRS. Conclusions. Gal-CSO/ATP nanoparticles have significant targeting efficiency in hepatic cells in vitro and enhancement efficiency of ATP peaks in HepG-2 cells. Furthermore, 31P MRS could be applied in the research of hepatic molecular imaging.

Hepatic mesenchymal hamartoma in a neonate with a Bochdalek diaphragmatic hernia: A case report

The Bochdalek diaphragmatic hernia (BDH) is a common birth defect that is associated with other congenital malformations. Hepatic mesenchymal hamartoma (HMH) is the second most common benign hepatic tumor in children. The association between BDH and HMH or ectopic hepatic tissue is uncommon. We report a case of a female newborn with a left BDH that at surgery was incidentally found to have a tumor of 3.5cm in maximum dimension with a serous muscular membrane. The histopathological study revealed vascular–mesenchymal stroma with bile ducts entrapped and peripheral normal hepatic tissue. These findings correlate with the diagnosis of hepatic mesenchymal hamartoma (HMH) in ectopic hepatic tissue. Our objective is to report a case of a rare association between HMH and BDH as well as discuss its differential diagnosis.

The Expression and Clinical Significance of Omi/Htra2 in Hepatocellular Carcinoma

To investigate Omi/HtrA2 expression and its clinical significance in hepatocellular carcinoma. We analyzed Omi/HtrA2 expression in hepatocellular carcinoma, paracancerous tissues and normal hepatic tissues by immunohistochemistry, RT-PCR and Western blot. Hypoxia-inducible factor-1α (HIF-1α) expression was also detected in hepatocellular carcinoma samples by immunohistochemistry. Meanwhile, we retrospectively analyzed the relationship between Omi/HtrA2 expression and the survival times of the patients. We found that Omi/HtrA2 overexpressed in hepatocellular carcinoma and was correlated with hepatocellular carcinoma differentiation, tumor size, portal vein invasion, clinical stage and lymph node metastasis. We also observed a significant inverse correlation between the expression of Omi,/HtrA2 and HIF-1α in hepatocellular carcinoma. The Kaplan-Meier estimates showed that patients who were Omi/HtrA2 positive had much longer survival times than those who were Omi/HtrA2 negative. Both univariate and multivariate analysis using the Cox regression model indicated that Omi/HtrA2 expression was a significant factor for prognosis. Hepatocellular carcinoma cells may need Omi/HtrA2 expression for apoptosis and Omi/HtrA2 might be an important prognostic marker for primary hepatocellular carcinoma.

MiR-106b downregulates adenomatous polyposis coli and promotes cell proliferation in human hepatocellular carcinoma

Aberrant activation of the Wnt/β-catenin signal pathway is frequently observed in hepatocellular carcinoma (HCC). β-Catenin is the major cellular effector of Wnt signaling and inactivation of adenomatous polyposis coli (APC) results in nuclear accumulation of β-catenin. Therefore, it was speculated that APC inhibition could play important roles in activating the Wnt/β-catenin pathway and in HCC progression. In this study, we report that miR-106b expression is markedly upregulated in hepatoma cells and hepatoma tissues compared with immortalized normal liver epithelial cells and normal hepatic tissues. Ectopic expression of miR-106b induces the proliferation and anchorage-independent growth of hepatoma cells, whereas inhibition of miR-106b reduced this effect. Furthermore, miR-106b upregulation in hepatoma cells modulated entry into the G(1)/S transitional phase by upregulating cyclin D1 and downregulating APC. Moreover, we demonstrated that miR-106b downregulates APC expression by directly targeting the 3'-untranslated region of APC messenger RNA. Taken together, our results suggest that miR-106b plays an important role in promoting the proliferation of human hepatoma cells and presents a novel mechanism of micro RNA-mediated direct suppression of APC expression in cancer cells.

Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 °C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 °C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

Expression of TAP1 and TNF-α in HBV-related hepatocellular carcinoma and its clinical significance

Objective To explore the association of expression of transporter associated with antigen processing（TAP1 ）, tumor necrosis factor-alpha （TNF-ot） with occurrence and development of HBV-related hepatocellular carcinoma（HCC）. Methods The expression of TAP1 and TNF-a in 35 liver carcinoma tissues, and 10 normal liver tissues were detected with immunohistochemical EnVision method,The expression and clinical significance of TAP1, TNF-a in HBV-related HCC were analyzed. Furthermore, the association of respective expression quantity with pathological typing of HCC was analyzed. Results The expression of TAP1 ,TNF-a was negative in hepatocytes of normal liver tissues. 91.4% of HCC tissues expressed TAP1. There was significantly statistical difference in expression of TAP1 between HCC tissues and the normal hepatic tissues（P 〈0.05） ;60% of HCC tissues expressed TNF-a. There was statistical difference in expression of TNF-a between HCC and the normal hepatic tissues （ P 〈 0. 05 ）, and the positive expression rate of TNF-a in well-differenciated HCC tissues was significantly higher than that in poorly-differenciated ones （P 〈 0. 05 ）. Conclusion TAPl-related MHC- I restricted antigen processing pathway was possibly normal in HBV-related HCC. The expression quantity of TNF-a was associated with the occurrence and degree of pathological differentiation of HBV-related HCC. Key words: Hepatitis B virus ; Hepatocellular carcinoma; Expression