Improved Recovery of Exfoliated Colonocytes from Feces Using Newly Developed Immunomagnetic Beads

We demonstrated the feasibility of a new methodology for isolating colonocytes from feces. To reduce costs and improve the recovery rate of colonocytes from feces, we attempted to develop new immunomagnetic beads. Several sizes of magnetic beads were prepared and tagged with a monoclonal antibody against EpCAM. We made several new monoclonal antibodies against EpCAM, and each monoclonal antibody was tagged to the magnetic beads. In the simulation, the most efficient recovery of HT-29 cells was obtained using the smallest size of beads. Also, beads tagged with a monoclonal antibody with a higher affinity against EpCAM had a higher recovery rate. Similar results were obtained when the smallest size of beads with the highest-affinity monoclonal antibody was applied to clinical samples. The newly developed immunomagnetic beads may be useful for isolating colorectal cancer cells from feces, enabling the cytological or molecular biological diagnosis of CRC

A case of pancreatic acinar cell carcinoma metastatic to skin

We report a rare case of pancreatic acinar cell carcinoma with widespread metastases in a 68-year-old woman who presented with subcutaneous nodules as the initial symptom. Computed tomography showed a pancreatic mass with hepatic tumors and enlarged lymph nodes besides ring-enhanced subcutaneous nodules. Magnetic resonance diffusionweighted imaging detected the presence of lesions in other organs. Histological analysis of a colonic polypoid lesion revealed carcinoma with endocrine and acinar differentiation compatible with pancreatic origin. Regrettably, she died of a cerebral infarction without any treatment, and autopsy findings confirmed our diagnosis

Lipopolysaccharide induces bacterial autophagy in epithelial keratinocytes of the gingival sulcus.

BACKGROUND:Interactions of resident bacteria and/or their producing lipopolysaccharide (LPS) with sulcular epithelial keratinocytes may be regulated by autophagy in the gingival sulcus. In this study, we investigated an induction of bacterial autophagy in exfoliative sulcular keratinocytes of the gingival sulcus and cultured keratinocytes treated with Porphyromonas gingivalis-originated LPS (PgLPS).RESULTS:Exfoliative sulcular keratinocytes showed an induction of autophagy, in addition to increased expression of LPS-mediated factors including lipopolysaccharide-binding protein and toll-like receptors (TLRs), leading to co-localization of bacteria with autophagosomes. In contrast, exfoliative keratinocytes from the free gingiva did not show similar autophagy. Autophagy activity in human cultured keratinocyte cells (HaCaT) was induced by PgLPS, which was dependent partially on the AMP-activated protein kinase (AMPK) pathway via increased intracellular reactive oxygen species (ROS) and was in association with an activation of TLR4 signaling. After incubation of cultured keratinocytes with E.coli BioParticles following PgLPS stimulation, co-localization of bioparticles with autophagosomes was enhanced. Conversely, blockage of autophagy with 3-methyladenin and LPS-binding with polymyxin B led to significant reduction of co-localization of particles with autophagosomes.CONCLUSION:These findings indicate that PgLPS-induced autophagy is at least partially responsible for interaction between bacteria and sulcular keratinocytes in the gingival sulcus.福岡歯科大学2018年

Low Concentration of Etoposide Induces Enhanced Osteogenesis in MG63 Cells via Pin1 Activation

福岡歯科大学2020年

Oxidative Stress-induced Interaction between Autophagy and Cellular Senescence in Human Keratinocytes

福岡歯科大学2017年

Bone Morphogenetic Protein-2 Accelerates Osteogenic Differentiation in Spheroid-Derived Mesenchymal Stem Cells

福岡歯科大学2018年

Susceptibility of the Wnt/β-catenin Pathway Accelerates Osteogenic Differentiation of Human Periodontal Ligament Stem Cell Spheroids

福岡歯科大学2018年

Blockade of constitutively activated ERK signaling enhances cytotoxicity of microtubule-destabilizing agents in tumor cells.

The extracellular signal-regulated kinase (ERK) signaling pathway is constitutively activated in many human tumor cell types. Given the cytoprotective role of this pathway, we examined whether its specific blockade might sensitize human tumor cells to the induction of apoptosis by various anticancer drugs. Although blockade of ERK signaling alone did not induce substantial cell death, it resulted in marked and selective enhancement of the induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the ERK pathway is constitutively activated. The synergistic activation of c-Jun NH(2)-terminal kinase by the combination of an ERK pathway inhibitor and a microtubule-destabilizing agent appeared to be responsible, at least in part, for this effect. These results suggest that administration of the combination of an ERK pathway inhibitor and a microtubule-destabilizing agent is a potential chemotherapeutic strategy for the treatment of tumor cells with constitutive activation of the ERK pathway

HTLV-1 bZIP Factor Induces T-Cell Lymphoma and Systemic Inflammation In Vivo

Human T-cell leukemia virus type 1 (HTLV-1) is the causal agent of a neoplastic disease of CD4+ T cells, adult T-cell leukemia (ATL), and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, and inflammatory lung diseases. ATL cells, which constitutively express CD25, resemble CD25+CD4+ regulatory T cells (Treg). Approximately 60% of ATL cases indeed harbor leukemic cells that express FoxP3, a key transcription factor for Treg cells. HTLV-1 encodes an antisense transcript, HTLV-1 bZIP factor (HBZ), which is expressed in all ATL cases. In this study, we show that transgenic expression of HBZ in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice, resembling diseases observed in HTLV-1 infected individuals. In HBZ-transgenic mice, CD4+Foxp3+ Treg cells and effector/memory CD4+ T cells increased in vivo. As a mechanism of increased Treg cells, HBZ expression directly induced Foxp3 gene transcription in T cells. The increased CD4+Foxp3+ Treg cells in HBZ transgenic mice were functionally impaired while their proliferation was enhanced. HBZ could physically interact with Foxp3 and NFAT, thereby impairing the suppressive function of Treg cells. Thus, the expression of HBZ in CD4+ T cells is a key mechanism of HTLV-1-induced neoplastic and inflammatory diseases