Search

Hepatocellular carcinoma (HCC), one of the most common types of liver cancer, could be treated with 5-fluorouracil (5-FU). Due to its side effects, 5-FU is more often used as the co-administration drug in clinical practice. Secalonic acid-F (SAF), isolated from a fungal strain identified in our lab as Aspergillus aculeatus, showed potent biological activities. The goal of this study was to evaluate the inhibitory effects of SAF on hepatocellular carcinoma and to compare it with that of 5-FU. Results showed that SAF effectively inhibited cell growth with a dose-dependent manner in vitro and in vivo. And the inhibitory effects of SAF were stronger than that of 5-FU. Importantly, the cytotoxicity of SAF to peripheral blood mononuclear cells (PBMC) was similar to that of 5-FU. Furthermore, this study demonstrated that SAF arrested the cell cycle at the G1 phase and induced apoptosis with a dose-dependent manner by activating caspase3 and caspase9 through a mitochondrial pathway. Consequently, SAF may be a better potential candidate compound for human cancer treatment; these results will afford more data for antitumor agent design in detail.

Background: Hepatocellular carcinoma (HCC) is a lethal disease, while the precise underlying molecular mechanisms of HCC pathogenesis remain to be defined. MicroRNA (miRNA), a class of non-coding small RNAs, can post-transcriptionally regulate gene expression. Altered miRNA expression has been reported in HCCs. This study assessed expression and the oncogenic activity of miRNA-10b (miR-10b) in HCC., Methods: Forty-five paired human HCC and adjacent non-tumor tissues were collected for qRT-PCR and immunohistochemistry analysis of miR-10b and CUB and Sushi multiple domains 1 (CSMD1), respectively. We analyzed the clinicopathological data from these patients to further determine if there was an association between miR-10b and CSMD1. HCC cell lines were used to assess the effects of miR-10b mimics or inhibitors on cell viability, migration, invasion, cell cycle distribution, and colony formation. Luciferase assay was used to assess miR-10b binding to the 3'-untranslated region (3'-UTR) of CSMD1., Results: miR-10b was highly expressed in HCC tissues compared to normal tissues. In vitro, overexpression of miR-10b enhanced HCC cell viability, migration, and invasion; whereas, downregulation of miR-10b expression suppressed these properties in HCC cells. Injection of miR-10b mimics into tumor cell xenografts also promoted xenograft growth in nude mice. Bioinformatics and luciferase reporter assay demonstrated that CSMD1 was the target gene of miR-10b. Immunocytochemical, immunohistochemical, and qRT-PCR data indicated that miR-10b decreased CSMD1 expression in HCC cells., Conclusions: We showed that miR-10b is overexpressed in HCC tissues and miR-10b mimics promoted HCC cell viability and invasion via targeting CSMD1 expression. Our findings suggest that miR-10b acts as an oncogene by targeting the tumor suppressor gene, CSMD1, in HCC.

The molecular pathogenesis of hepatocellular carcinoma (HCC) is heterogeneous and extremely complex. Thus, for individual molecular targeted therapy, novel molecular markers are needed. The abnormal expression of the human homolog of Drosophila headcase (HECA homo) has been found in pancreatic, colorectal, and oral squamous cell carcinoma. Studies of oral squamous cell carcinoma have also demonstrated that the HECA homo protein can be negatively controlled by the Wnt-pathway and transcription factor 4 (TCF4) and can slow cell division by interacting with cyclins and CDKs. However, the role of HECA in HCC has not been reported elsewhere. Here, immunohistochemical analysis revealed that the downregulation of HECA homo protein occurred in 71.0% (66/93) of HCC cases and was positively correlated with a poorly differentiated grade, high serum AFP level, liver cirrhosis and large tumor size. The expression of HECA homo was detected in five live cell lines. In vitro, the overexpression of HECA homo in HepG2, Huh-7 and MHCC-97H cells could inhibit cell proliferation and colony formation and induce G1 phase arrest. In contrast, the downregulation of HECA homo could promote cell proliferation, colony formation and the cell cycle process. However, neither the overexpression nor downregulation of HECA homo in the three cell lines could affect cell migration or invasion. Collectively, HECA homo is regularly expressed in normal live cells, and the HECA homo protein level is heterogeneously altered in HCC, but the downregulation of HECA homo is more common and positively correlated with several malignant phenotypes. The HECA homo protein can slow cell proliferation to some extent primarily through its blocking effect on the cell cycle. Hence, the HECA homo protein may act as a tumor suppressor in HCC and might be a potential molecular marker for diagnostic classification and targeted therapy in HCC.

Platycodin D (PD), a triterpenoid saponin isolated from Platycodonis Radix, is a famous Chinese herbal medicine that has been shown to have anti-proliferative effects in several cancer cell lines. The aim of this study was to determine the changes in cellular proteins after the treatment of hepatocellular carcinoma HepG2 cells with PD using proteomics approaches. The cell viability was determined using the MTT assay. The proteome was analyzed by two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Western blot analysis was used to confirm the expression of changed proteins. Our results showed that PD inhibited the proliferation of HepG2 cells in concentration- and time-dependent manners. Sixteen proteins were identified to be up-regulated in PD-treated HepG2 cells, including ATP5H, OXCT1, KRT9, CCDC40, ERP29, RCN1, ZNF175, HNRNPH1, HSP27, PA2G4, PHB, BANF1, TPM3, ECH1, LGALS1, and MYL6. Three proteins (i.e., RPS12, EMG1, and KRT1) decreased in HepG2 cells after treatment with PD. The changes in HSP27 and PHB were further confirmed by Western blotting. In conclusion, our results shed new lights on the mechanisms of action for the anti-cancer activity of PD., (Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study is to identify the gene expression profile specific to Hepatocellular Carcinoma (HCC) by comparing the different expression profiles in cirrhosis, dysplastic nodule (DN) and HCC tissues., Materials and Methods: The microarray data were downloaded from Gene Expression Omnibus (GEO) repository, involving 39 samples of normal liver tissues, 33 samples of cirrhosis, 17 samples of DNs and 286 samples of HCCs of different stages. Differential Expressed Genes (DEGs) of cirrhosis, DN and HCC liver tissues were analyzed by BRB-ArrayTool software; besides, the Gene Ontology (GO) analysis, Kyoto encyclopedia of Genes and Genomes (KEGG) and Biocarta pathway enrichment analysis were also performed. A protein-protein interaction (PPI) network was then constructed by STRING software using the genes in significantly different pathways. The resulting network was analyzed by Cytoscape software with CentiScaPe plugin to calculate the topological characteristics of the network and its individual node. Key genes were screened according to betweenness and degree of nodes., Results: few overlaps occurred in the GO categories of DEGs and in the gene sets from pathway analysis between HCCs, cirrhosis and DNs. DEGs in abnormal tissues were shown to be enriched in 29 KEGG pathways and 18 Biocarta pathways; and 43 key genes were identified to be involved in the maintenance of PPI network. In addition, the gene expression profiles were significantly different among cirrhosis, DN and HCC tissues., Conclusions: The bioinformatic analysis of GEO datasets of HCC identified the functional gene sets associated with the genesis and development of HCC, and the key genes that were playing important roles in the maintenance of the molecular network for biological function specific to HCC. It provides the insights for more precise understandings of pathogenic mechanism, which will further expand the study on biomarker and targeted therapy of HCC.

Objective: To study the antiangiogenetic and tumor inhibitory effects of endostatin (Es) by intratumoral versus intravenous administration combined with adriamycin (Adm) for treatment of transplanted tumor in mice., Methods: Forty mice were subjected to subcutaneous implantation of H22 cells and randomly divided into 4 groups by the body weight when the tumor diameter reached 1 cm, namely the control group (with intratumoral and intravenous injection of normal saline), Es intratumoral group (with intratumoral injection Es and intraperitoneal Adm injection), Es vein group (with intravenous Es injection and intraperitoneal Adm injection), and Adm group (with intratumoral saline injection and intraperitoneal Adm injection). The tumor volumes and tumor inhibition rates were calculated, and the expression of vascular endothelial growth factor (VEGF) and the microvessel density (MVD) of the tumors were examined, with the survival time of the mice also observed., Results: The tumor volume was smaller in Es intratumoral group than in the other groups (P<0.05). The expression of VEGF and M VD in Es intratumoral group was significantly decreased as compared with that in the other groups (P<0.05). The survival time was significantly longer in Es intratumoral group and Es vein group than in the other groups (P<0.05), but showed no significant difference between Es intratumoral group and Es vein group (P>0.05)., Conclusion: In combination with Adm regimen, Es given intratumoral injection produces better effect than intravenous Es injection against angiogenesis and tumor growth, no significant difference can be found in the survival time between them.

Objective: To study the changes of immune function in patients with liver cancer after transcatheter arterial chemoembolizaton (TACE) combined with interstitial therapy., Methods: Forty patients with liver cancer were randomly divided into groups A and B to received TACE and TACE combined with percutaneous lipiodol and anti-cancer agent injection into the tumor. The T lymphocyte cell subsets in the peripheral blood before and one week after the operation were measured by flow cytometry, and the immunoglobulin contents determined by single radial immunodiffusion., Results: CD3, CD4, and CD4/8 levels increased significantly after the operation in both groups A and B (P<0.05). The postoperative CD3 and CD4 levels, but not that of CD8, differed significantly between the two groups (P<0.05). The operations also resulted in an increase in the contents of the immunoglobulins and complements in the two groups, but the changes were not significant in group A (P>0.05); in group B, significant increases occurred in the immunoglobulin and complement levels (P<0.05) with the exception of C3., Conclusion: The combination of TACE and interstitial therapy with percutaneous intratumor injections of lipiodol and anti-cancer agents may better improve the cell-mediated immunity and humoral immune function of liver cancer patients.

Objective: To Compare the therapeutic effects of cryocareTM cryoablation, radiofrequency ablation(RFA), and and microwave coagulation (MCT) in rabbits with VX(2) liver cancer., Methods: Forty-five rabbits with VX(2) liver cancer were randomly and equally allocated into 5 groups to receive treatment with cryocare cryoablation (group A), radiofrequency ablation (group B), microwave coagulation (group C), surgical resection (group D) and control group (group E), respectively. The residual tumor tissues and metastasis (intrahepatic, lung, abdominal lymphoid node, and abdominal implantation) were observed after the treatments, with also detection of soluble interleukin-2 receptor ( sIL-2R) and recording of the survival time of the rabbits., Results: Significant differences were found in the occurrence of tumor residue (chi(2)=20.700, P=0.0000), intrahepatic metastasis (chi(2)=15.652, P=0.0004), and abdominal implantation tumor (chi(2)=13.894, P=0.0008) between the 5 groups, but not in lung and abdominal lymph node metastasis. sIL-2R levels differed significantly only after but not before the treatments (F=31.58, P=0.000) between groups A to D and group E (t=10.119, P=0.000). The treatments in groups A to D all resulted in prolonged survival of the rabbits as compared with the control (F=73.084, P=0.000), and cryocareTM cryoablation and surgical resection showed similarly better effect than RFA and MCT., Conclusion: Cryocare cryoablation can be more effective than RFA and MCT in reducing tumor residue and metastasis and prolonging the survival time of rabbits with VX(2) liver cancer, and RFA and MCT are comparable for their therapeutic effects.

The clinical presentations and imaging characteristics of hepatocellular carcinoma (HCC) are usually various and complex. This article reported 2 cases of HCC with the initial symptoms being bone metastasis that did not exhibit typical clinical manifestations or distinct feature in liver imaging, without elevated serum alpha-fetoprotein. The diagnoses were certified by fine needle aspiration biopsy, which is recommended for differential diagnosis in cases of complex HCC with bone metastasis, to avoid liver biopsy and surgical bone biopsy.