Sorafenib combined with dasatinib therapy inhibits cell viability, migration, and angiogenesis synergistically in hepatocellular carcinoma.

Purpose: Sorafenib is a multikinase inhibitor used for treatment of advanced hepatocellular carcinoma. Sorafenib resistance may be related to Src-induced cell migration and angiogenesis, which are regulated by cancer stem cell activation and release of vascular endothelial growth factor. Dasatinib is a Src inhibitor that inhibits Src phosphorylation and suppresses Src-associated cell migration and angiogenesis.

The Roles Of Angiogenesis And Cancer Stem Cells In Sorafenib Drug Resistance In Hepatocellular Carcinoma.

Background: An increasing number of studies support cancer stem cells as the reason for chemoresistance to sorafenib therapy in hepatocellular carcinoma (HCC), but the mechanism is still unclear. In this study, the mechanism of sorafenib resistance in cancer stem cells was examined by in vitro experiments and xenograft mouse model.

Methods: The expression of cancer stem cell markers in the Chang liver cell line and PLC/PRF/5 and HepG2 hepatoma cell lines were compared by immunoblot assay before and after sorafenib treatment in vitro.

The Prognostic Value of Cytokeratin and Sal-Like Protein 4 Expression in Hepatocellular Carcinoma and Intra-Hepatic Cholangiocarcinoma in Taiwan.

We previously reported that modulation of cytokeratin18 induces pleomorphism of liver cells, higher cell motility, and higher drug sensitivity to sorafenib treatment of hepatoma cells. These relationships were established by experiments. The aim of this study was to determine the association between cytokeratin expression and tumor behavior, as well as cancer stem cells of hepatocellular carcinoma and intra-hepatic cholangiocarcinoma in Taiwan.

Cytokeratin 18-associated Histone 3 Modulation in Hepatocellular Carcinoma: A Mini Review.

Unstable cytokeratins are associated with tumor transformation in the development of human hepatocellular carcinoma. We previously demonstrated that the cytokeratin 18 was modulated and that a histone H3-specific modification occured, among members of the histone family, during the development of human hepatocellular carcinoma. Evidence suggested that the modification of histone H3 was highly correlated with the modulation of cytokeratin 18 and probably plays an important role in tumorigenesis of hepatocytes.

Plectin deficiency in liver cancer cells promotes cell migration and sensitivity to sorafenib treatment.

Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma.

Cell Pleomorphism and Cytoskeleton Disorganization in Human Liver Cancer.

Background/aim: Nucleoskeleton maintains the framework of a cell nucleus that is required for a variety of nuclear functions. However, the nature of nucleoskeleton structure has not been yet clearly elucidated due to microscopy visualization limitations. Plectin, a nuclear pore-permeable component of cytoskeleton, exhibits a role of cross-linking between cytoplasmic intermediate filaments and nuclear lamins.

Hypoacetylation in association with histone 3 modulation in human hepatocellular carcinoma.

Background: Aberrant histone deacetylase expression may cause imbalance between acetylation and deacetylation of histone and play roles in tumor transformation. We found that histone 3 was modulated in human hepatocellular carcinoma. We determined if histone 3 modulation is related to the aberrant expression of histone deacetylase.

Transient knockdown-mediated deficiency in plectin alters hepatocellular motility in association with activated FAK and Rac1-GTPase.

Background: Plectin is one of the cytolinker proteins that play a crucial role in maintaining the integrity of cellular architecture. It is a component of desmosome complexes connecting cytoskeletal proteins and trans-membrane molecules. In epithelial cells, plectin connects cytokeratins and integrin α6β4 in hemidesmosomes anchoring to the extracellular matrix.

Plectin deficiency on cytoskeletal disorganization and transformation of human liver cells in vitro.

Plectin is a versatile cytoplasmic cross-linking protein that connects intermediate filaments to microfilaments, microtubules, and membrane adhesion sites. The cross-linking functions of plectin help organize the cytoskeleton into a stable meshwork important for maintaining uniformity in cell size and shape. As cells of hepatocellular carcinoma are morphologically different from normal human hepatocytes, we hypothesized that altered plectin expression and cytoskeletal organization underlies this pleomorphic transformation.

Cytokeratin 18-mediated disorganization of intermediate filaments is induced by degradation of plectin in human liver cells.

Plectin is a cross-linking protein that organizes the cytoskeleton into a stable meshwork that helps maintain the uniform size and shape of cells. As cells of hepatocellular carcinoma are morphologically different from healthy human hepatocytes, we hypothesized that plectin deficiency and cytoskeletal disorganization underlies this pleomorphic transformation. To test this hypothesis we induced apoptosis as the most accessible pathway for creating plectin deficiency status in vivo.

Synemin down-regulation in human hepatocellular carcinoma does not destabilize cytoskeletons in vivo.

Synemin is a large intermediate filament protein that has been identified in all types of muscle cells. It plays a role in human muscle diseases; however, the role of synemin in tumor cell transformation has rarely been investigated. Because hepatocellular carcinoma cells are morphologically different from normal human hepatocytes, we hypothesized that altered synemin expression and cytoskeletal disorganization might underlie this pleomorphic transformation.

Degradation of plectin with modulation of cytokeratin 18 in human liver cells during staurosporine-induced apoptosis.

Background: Hepatoma cells are morphologically different from those of the normal liver. Intermediate filaments (IFs) are important in building the cellular architecture and maintaining the outline of cells. Plectin is a cross-linking protein that organizes the cytoskeleton into a stable meshwork, which can maintain the uniform size and shape of hepatocytes.

Possible relation between histone 3 and cytokeratin 18 in human hepatocellular carcinoma.

Background: Previously we found some low molecular weight proteins identified as histone in hepatocelluar carcinoma. Our objective was to clarify whether the coimmunoprecipitation of histone and cytokeratin 18 was an artifact or not.

Materials And Methods: Histone 3 and cytokeratin 18 were investigated in three cases of human hepatocellular carcinoma and one case of normal liver tissue.

Altered synemin could affect the organization of intermediate filament in human hepatocellular carcinoma.

Cells of human hepatocellular carcinoma (HCC) were morphologically different from those of normal liver. Intermediate filaments are important in building the architecture of liver cells and are proposed to interact with other cellular components. Synemin is one of intermediate filament associated proteins which can link between intermediate filament and other cytoskeletal structures.

An early evaluation of malignant tendency with plectin expression in human colorectal adenoma and adenocarcinoma.

Tumor cells are morphologically different from normal cells. In this situation, we proposed that plectin, one of the intermediate filament associated proteins, might play some special roles in the tumorigenesis. Plectin exhibits a wide distribution spectrum among various tissues; however, it is scarcely investigated in tumor tissues including colorectal adenocarcinoma.

The influence of plectin deficiency on stability of cytokeratin18 in hepatocellular carcinoma.

Intermediate filaments are important in building the cellular architecture. Previously we found cytokeratin18 was modulated in human hepatocellular carcinoma. Plectin is a cross-linking protein that organizes the cytoskeleton into a stable meshwork, which can maintain the uniform size and shape of hepatocytes.

Effects of diode 808 nm GaAlAs low-power laser irradiation on inhibition of the proliferation of human hepatoma cells in vitro and their possible mechanism.

Low-power laser irradiation (LPLI) has come into a wide range of use in medical field. Considering basic research, LPLI can enhance DNA synthesis and increases proliferation rate of human cells. But only a few data about the effects of LPLI on human liver or hepatoma cells are available.

Pleomorphism of cancer cells with the expression of plectin and concept of filament bundles in human hepatocellular carcinoma.

Intermediate filaments are important in building the architecture of liver cells and are proposed to interact with other cellular components. Among intermediate filament associated proteins, plectin is a versatile cytoskeletal linkage protein which has been shown to interact with a variety of cytoskeletal structures. Intermediate filament and plectin might play some roles in tumorigenesis of human hepatocellular carcinoma since cells of hepatocellular carcinoma were morphologically different from normal liver.

HCC CKs are altered histones during tumor transformation in hepatoma.

The stability of cytokeratin (CK) protein during tumor transformation in human hepatocellular carcinoma (HCC) was studied with molecular approach previously. The results demonstrated that the CK was modulated in human HCC. Besides this, three low molecular weight CK molecules (named HCC CK) were found.