Metabolic analysis of three-dimensional cultured gastrointestinal cancer cells suggests that L-arginine inhibits tumor growth by affecting the urea cycle.

Introduction: There is evidence for the anticancer effects of L-arginine (arginine); however, the direct effects on cancer cells and mechanism of action are unclear.

Methods: Various upper gastrointestinal cancer cells (OE19, OE33, MKN1, MKN45, MKN74, and AGS) were divided into arginine-treated and untreated groups and cultured using two-dimensional and three-dimensional culture systems. Proliferation was evaluated using the MTT assay to identify arginine-sensitive (OE33) and arginine-insensitive (OE19) strains.

Three-Dimensional Culture of Glioblastoma Cells Using a Tissueoid Cell Culture System.

In classical cell culture techniques, cancer cells typically proliferate in a single layer by adhering to the undersurface of laboratory vessels. Consequently, concerns have been raised regarding the fidelity of the morphological and functional characteristics of these cultured cancer cells compared to those of their counterparts. Our previous studies have investigated various epithelial malignant tumors utilizing the Tissueoid cell culture system, a three-dimensional (3D) cultivation method employing Cellbed-a nonwoven sheet composed of high-purity silica fibers as a scaffold.

Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems.

The conventional two-dimensional (2D) culture is available as an in vitro experimental model. However, the culture system reportedly does not recapitulate the in vivo cancer microenvironment. We recently developed a tissueoid cell culture system using Cellbed, which resembles the loose connective tissue in living organisms.

Similarities and differences in metabolites of tongue cancer cells among two- and three-dimensional cultures and xenografts.

Metabolic programming of cancer cells is an essential step in transformation and tumor growth. We established two-dimensional (2D) monolayer and three-dimensional (3D) cultures, the latter called a "tissueoid cell culture system", using four types of tongue cancer cell lines. We also undertook a comprehensive metabolome analysis of three groups that included xenografts created by transplanting the cell lines into nude mice.

Application of "Tissueoid Cell Culture System" Using a Silicate Fiber Scaffold for Cancer Research.

Background: We developed a 3-dimensional (3D) culture system using a high-purity silica fiber scaffold of unwoven sheets called CellbedTM.

Methods: We used adherent colon and esophagogastric junction adenocarcinoma cells, tongue squamous cell carcinoma (SqCC) cells, and nonadherent gastric cancer cells. These cells were subjected to staining with various substances and observed by electron microscopy.

Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.

Esophageal squamous cell carcinomas (ESCCs) as well as adenocarcinomas (EACs) were developed in rat duodenal contents reflux models (reflux model). The present study aimed to shed light on the mechanism by which bile acid stimulation causes cancer onset and progression. Metabolomics analyses were performed on samples of neoplastic and nonneoplastic tissues from reflux models, and K14D, cultivated from a nonmetastatic, primary ESCC, and ESCC-DR, established from a metastatic thoracic lesion.

Host factors influence Barrett's carcinogenesis: findings from a mouse gastroduodenal reflux model.

Background: Rat gastroduodenal reflux models have been used for analyzing Barrett's carcinogenesis. Mice seem to be more useful than rats for studies targeting genes.

Methods: We induced gastroduodenal contents reflux by esophagojejunostomy using C57BL/6J mice.

Opposite effects of two nonstructural proteins of Theiler’s murine encephalomyelitis virus regulates apoptotic cell death in BHK-21 cells.

Theiler’s murine encephalomyelitis virus is divided into two subgroups, TO and GDVII, inducing subgroup-specific diseases. In order to investigate the role(s) of nonstructural proteins of TMEV, L and L(∗), leaders of two subgroups, were separately expressed with or without L(∗) in BHK-21 cells. Expression of L increased the number of apoptotic cells.

Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells.

Bcl3 is a member of the IkappaB family that regulates genes involved in cell proliferation and apoptosis. Recent reports indicated that Bcl3 is overexpressed in HTLV-1-infected T cells via Tax-mediated transactivation, and acts as a negative regulator of viral transcription. However, the role of Bcl3 in cellular signal transduction and the growth of HTLV-1-infected T cells have not been reported.

Leader (L) of Theiler's murine encephalomyelitis virus (TMEV) is required for virus growth in a murine macrophage-like cell line.

Theiler's murine encephalomyelitis virus is divided into two subgroups on the basis of their different biological activities. GDVII subgroup strains cause acute and fatal encephalomyelitis in mice, while TO or DA subgroup strains cause non-fatal polioencephalomyelitis in weanling mice followed by virus persistence and demyelination in the spinal cords. Nonstructural leader (L) protein is encoded at the most N-terminus of the polyprotein.

Different subcellular localization of Theiler's murine encephalomyelitis virus leader proteins of GDVII and DA strains in BHK-21 cells.

The highly virulent GDVII strain of Theiler's murine encephalomyelitis virus causes acute and fatal encephalomyelitis, whereas the DA strain causes mild encephalomyelitis followed by a chronic inflammatory demyelinating disease with virus persistence. The differences in the amino acid sequences of the leader protein (L) of the DA and GDVII strains are greater than those for any other viral protein. We examined the subcellular distribution of DA L and GDVII L tagged with the FLAG epitope in BHK-21 cells.

Inhibition of colon cancer growth and metastasis by NK4 gene repetitive delivery in mice.

NK4, originally prepared as a competitive antagonist for hepatocyte growth factor (HGF), is a bifunctional molecule that acts as an HGF-antagonist and angiogenesis inhibitor. When the expression plasmid for NK4 gene was administered into mice by hydrodynamics-based delivery, the repetitive increase in the plasma NK4 protein level was achieved by repetitive administration of NK4 gene. Mice were subcutaneously implanted with colon cancer cells and weekly given with the NK4 plasmid.

CD300 antigen like family member G: A novel Ig receptor like protein exclusively expressed on capillary endothelium.

We report the characteristics of CD300LG, a member of the CD300 antigen like family. Its genomic structure is similar in both mouse and human, and at least four isoforms exist in both species. The amino acid sequence of the immunoglobulin (Ig) V like domain of CD300LG showed approximately 35% identity to those of the polymeric Ig receptor (pIgR) and Fcalpha/muR.

Hepatic gene expression of NK4, an HGF-antagonist/angiogenesis inhibitor, suppresses liver metastasis and invasive growth of colon cancer in mice.

Hepatocyte growth factor (HGF) is involved in malignant behavior of cancer cells by enhancing invasion and metastasis. We earlier found that NK4, a four-kringle fragment of HGF, functions as both an HGF antagonist and an angiogenesis inhibitor. We have now carried out studies to determine if hydrodynamics-based delivery and expression of the NK4 gene would inhibit liver metastasis and invasive growth of colon carcinoma cells in mice.