Up-regulation of Krüppel-like factor 8 promotes tumor invasion and indicates poor prognosis for hepatocellular carcinoma.

Background & Aims: The transcription factor Krüppel-like factor 8 (KLF8) has a role in tumor development, growth, and metastasis, but its role in hepatocellular carcinoma (HCC) is not clear.

Methods: KLF8 expression in human HCC cell lines and tumor tissues was measured by quantitative real-time polymerase chain reaction, immunoblot, and immunochemical analyses. The effects of KLF8 depletion or overexpression in HCC cells were observed in cultured cells and in mice.

Small interference RNA targeting Krüppel-like factor 8 inhibits the renal carcinoma 786-0 cells growth in vitro and in vivo.

Purpose: Krüppel-like factor 8 (KLF8) plays an important role in oncogenic transformation and is highly overexpressed in several types of human cancer. We investigated the expression of KLF8 in renal cell carcinoma (RCC) tissues and the role of small interference RNA targeting KLF8 on growth, cell cycle, and apoptosis of human renal carcinoma cell line 786-0 in vitro and in vivo.

Methods: The expression of KLF8 protein and mRNA in human renal carcinoma samples was detected by immunochemistry and reverse transcription polymerase chain reaction (RT-PCR).

Proteomic identification of a monoclonal antibody recognizing caveolin-1 in hepatocellular carcinoma with metastatic potential.

A monoclonal antibody, McAb9E (IgG3), was generated against a metastatic HCC cell line, MHCC-1. The antigen was characterized as human Caveolin-1 (Cav-1, 21kDa), with pI of 5.65.

Role of overexpression of CD151 and/or c-Met in predicting prognosis of hepatocellular carcinoma.

Unlabelled: It has been reported that tetraspanin CD151 acts as a promoter of metastasis in several tumors and plays an important role in c-Met/hepatocyte growth factor signaling. However, the role of CD151 alone and coexpression of CD151/c-Met in hepatocellular carcinoma (HCC) remains unclear. We found that expression of CD151 was positively related to metastatic potential of HCC cell lines, and modified cells with CD151(high) showed higher secretion of matrix metalloproteinase 9 and aggressiveness in vitro and higher metastatic ability in vivo.

Biological characteristics of fluorescent protein-expressing human hepatocellular carcinoma xenograft model in nude mice.

Objectives: To study biological characteristics of stable red fluorescent protein (RFP)-expressing or green fluorescent protein (GFP)-expressing HCCLM3 cell lines and those of their relevant xenograft models in nude mice.

Methods: HCCLM3, a human hepatocellular carcinoma cell line with high metastatic potential was infected with RFP or GFP full-length cDNA via lentivirus. Stable RFP-expressing or GFP-expressing HCCLM3 cells, namely HCCLM3-R and HCCLM3-G, were subcutaneously injected and two patient-like metastatic models of HCCLM3-R and HCCLM3-G in nude mice were established using surgical orthotopic implantation from subcutaneous tumor tissues.

[The effects of ezrin on the proliferation and the invasiveness of cells of different hepatocellular carcinoma cell lines].

Objective: To investigate the different expressions of cytoskeletal organizer ezrin and cytoskeleton protein beta- and gamma-actin in hepatocellular carcinoma (HCC) cell lines with different metastatic potentials and to explore the role of ezrin in cell growth and metastasis in HCC cell lines SF7721 and MHCC97-H.

Methods: Immunofluorescence, RT-PCR and Western blot were used to detect the gene and protein expressions of ezrin and actin in hepatocellular carcinoma cell lines with different metastatic potentials. RNA interference (RNAi) was applied to down-regulate the ezrin expression in SF7721 and MHCC97-H.

The membrane-cytoskeleton organizer ezrin is necessary for hepatocellular carcinoma cell growth and invasiveness.

Purpose: The change of cell mobility is one of the preconditions of tumor metastasis. Cell skeleton alteration and rearrangement of F-actin was closely related to cell mobility. Ezrin is a membrane-cytoskeleton organizer that can mediate the rearrangement and the function of F-actin.

[The influence of downregulation of ezrin expression by RNA interference on the growth and metastasis of hepatocellular carcinoma: experiment in vitro].

Objective: To investigate the effect of membrane-cytoskeleton linker ezrin on the growth and metastasis of human hepatocellular carcinoma cell (HCC) lines.

Methods: Human HCC cells of the lines SF/SMMC7721, MHCC97-H, MHCC-1, and HepG2 were cultured. Four pairs of small interfering RNA (siRNA) targeting erzin were designed and transfected into the HCC cells.

[Reconstructing the JAK/STATs signal pathway restored the anti-proliferative response of MHCC97 on interferon alpha].

Objective: To elucidate the roles of JAK/STATs signal pathway on anti-proliferative effects induced by IFN-alpha in MHCC97.

Methods: An IRF9 expression vector was transfected into MHCC97 with Dosper. The expression of IRF9, cycle regulating proteins and the forming of ISGF3 complex were detected using Western blot and EMSA, respectively.

Modulation of gene expression in MHCC97 cells by interferon alpha.

Aim: To elucidate the molecular mechanisms of the inhibitory effects of IFN-alpha on tumor growth and metastasis in MHCC97 xenografts.

Methods: Three thousand international units per milliliter of IFN-alpha-treated and -untreated MHCC97 cells were enrolled for gene expression analysis using cDNA microarray. The mRNA levels of several differentially expressed genes in cDNA microarray were further identified by Northern blot and RT-PCR.

Reduction in p48-ISGFgamma levels confers resistance to interferon-alpha2a in MHCC97 cells.

Objectives: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in China and, due to the limited efficacy of currently available therapies, is responsible for a large number of deaths. IFN-alpha therapy has shown promise in the treatment of various forms of human cancer and is considered in the treatment of HCC. Previous results from our group showed that high doses of IFN-alpha exert a significant antiproliferative effect on MHCC97 human xenografts in nude mice, but not on MHCC97 cells when tested in vitro.

Interferon alpha 2a down-regulates VEGF expression through PI3 kinase and MAP kinase signaling pathways.

An earlier report demonstrated that interferon alpha (IFN-alpha) inhibited tumor growth and recurrence in an MHCC97 xenograft model in nude mice by suppressing tumor angiogenesis rather than by inhibiting tumor cell proliferation. However, the underlying molecular mechanism was not fully elucidated. In this study, we demonstrated that IFN-alpha 2a could down-regulate VEGF expression both in mRNA and in protein levels, as well as down-regulating HIF-1 alpha mRNA expression in MHCC97 cells in vitro.

A decade's studies on metastasis of hepatocellular carcinoma.

Metastasis remains one of the major challenges before hepatocellular carcinoma (HCC) is finally conquered. This paper summarized a decade's studies on HCC metastasis at the Liver Cancer Institute of Fudan University. We have established a stepwise metastatic human HCC model system, which included a metastatic HCC model in nude mice (LCI-D20), a HCC cell line with high metastatic potential (MHCC97), a relatively low metastatic potential cell clone (MHCC97L) and several stepwise high metastatic potential cell clones (MHCC97H, HCCLM3, and HCCLM6) from their parent MHCC97 cell.

[Influence of the inhibitor of c-Met on the growth and motility of hepatocellular carcinoma cells].

Objectives: To explore the influence of c-Met inhibitor by synthetic c-Met antisense oligonucleotide, constructive c-Met antisense plasmid and the complex plasmid of U1SnRNA/ ribozyme/anti-Met on the growth and metastasis of hepatocellular carcinoma cells.

Methods: Gene transfection was operated by Lipofectin on SF7721 cells. The difference of the cells before and after transfection was compared by MTT, growth curves and transwell test in vitro.

Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice.

The aim of this study was to examine the mechanism of interferon alpha (IFN-alpha) on inhibition of metastasis and recurrence of hepatocellular carcinoma (HCC). Nude mice bearing human HCC xenografts with high metastatic potential (LCI-D20) underwent curative resection of tumors on postimplant day 11. IFN-alpha was begun the next day at different dosages given subcutaneously for 35 consecutive days; normal saline solution was injected into the control mice.

Comparison between radioimmunotherapy and external beam radiation therapy for patients with hepatocellular carcinoma.

It has previously been observed in animal studies that, at equivalent doses, radioimmunotherapy (RIT) is 2.5 times more effective than multiple fractions of external beam radiation therapy (EBRT) in inhibiting tumour growth. In this study, we compared the use of RIT and EBRT in patients with hepatocellular carcinoma (HCC), treated during the past 10 years.

Construction and preliminary screening of a human phage single-chain antibody library associated with gastric cancer.

Background: The aim of this study was to construct a phage library of human single-chain antibodies associated with gastric cancer and screen such a library for CEA binding scFv.

Materials And Methods: The cDNA library of antibody variable regions was constructed using mRNA from metastatic lymph nodes or spleen of patients with stomach cancer by RT-PCR. These cDNA were assembled into a single-chain format and cloned into phagemid pCANTAB-5 and then transformed into Escherichia coli TG1.

Tumor radioimmunoimaging of chimeric antibody in nude mice with hepatoma xenograft.

AIM:To study the radioimmunoimaging (RAII) using the human/mouse chimeric Ab to evaluate its targeting activity in animal models.METHODS: To chimeric Ab was labeled with (131)I. RAII was performed at different intervals after injection of radio-labeled Abs in nude mice with human hepatoma xenograft, and tissue distribution of radioactivity was measured.

Multimodality treatment of hepatocellular carcinoma.

By 1996, 2898 patients with pathologically proven hepatocellular carcinoma (HCC) had been treated at the Liver Cancer Institute of Shanghai Medical University. The 5 year survival in the entire series was 36.2%, being increased from 4.