- S100 Proteins and Annexins
- Occupational and environmental lung diseases
- Tissue Engineering and Regenerative Medicine
- Medical Imaging and Pathology Studies
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Lung Cancer Treatments and Mutations
- Liver physiology and pathology
- Immune Response and Inflammation
- Cancer Research and Treatments
- Pancreatic function and diabetes
- Neonatal Respiratory Health Research
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- Cancer, Hypoxia, and Metabolism
- Protease and Inhibitor Mechanisms
- Advanced Glycation End Products research
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related gene regulation
- Endoplasmic Reticulum Stress and Disease
- Cancer Genomics and Diagnostics
- Antimicrobial Peptides and Activities
- Organ Transplantation Techniques and Outcomes
- RNA modifications and cancer
Okayama University
2016-2025
Institute of Cell Biology
2014-2020
Graduate School USA
2020
Okayama Shoka University
2011-2019
Okayama University Hospital
2017-2018
Kyushu University
2013
Kyoto University
2013
Kawasaki Medical School
2013
Tokyo Medical University
2012
Okayama Rosai Hospital
2011
Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before transplantation can be performed. Transplantation isolated hepatocytes has been proposed for the temporary metabolic support awaiting or spontaneous reversion their disease. A major limitation this form therapy is present inability to isolate an adequate number transplantable hepatocytes. highly differentiated cell line, NKNT-3, was generated by retroviral transfer normal primary...
The receptor for advanced glycation end products (RAGE) is thought to be involved in the pathogenesis of a broad range inflammatory, degenerative and hyperproliferative diseases. It binds diverse ligands activates multiple intracellular signaling pathways. Despite these pivotal functions, molecular events just downstream ligand-activated RAGE have been surprisingly unknown. Here we show that cytoplasmic domain phosphorylated at Ser391 by PKCζ upon binding ligands. TIRAP MyD88, which are...
Abstract Alteration in genes which takes place during malignant conversion and progression could be potential targets for gene therapy. We previously identified REIC/Dkk-3 as a whose expression is reduced many human cancers. Here, we showed that of was consistently prostate cancer tissues stage-dependent manner. Forced induced apoptosis cell lines lacking endogenous but not REIC/Dkk-3-proficient normal epithelial stromal cells. The involved c-Jun-NH2-kinase activation, mitochondrial...
The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation metastasis. However, receptor(s) mediating physiologic pathophysiologic effects this damage-associated "danger signal" are uncertain. In study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound but not...
Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause autosomal recessive forms Parkinson's disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and it protects cells from oxidative stresses. Although there has been considerable progress in elucidation various aspects protein regulation such as activation, stability degradation, transcriptional mRNA under stress conditions remains unclear. In this study, we found...
Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal prognosis. Unlike other malignancies, TP53 mutations are rare in MPM. Recent studies have showed that altered expression of microRNA (miRNA) observed human malignant tumors. In this study, we investigated the alterations miR-34s, direct transcriptional target TP53, and role miR-34s on pathogenesis MPM.Aberrant methylation were examined MPM cell lines miR-34b/c was transfected to cells estimate protein expression,...
We encountered a family of Japanese descent in which multiple members developed lung cancer. Using whole-exome sequencing, we identified novel germline mutation the transmembrane domain human epidermal growth factor receptor 2 ( HER2 ) gene (G660D). A somatic (V659E) was also detected one 253 sporadic adenocarcinomas. Because is considered to be responsible for dimerization and subsequent activation HER downstream signaling pathways, performed functional analyses these mutants. Mutant G660D...
Background. Cholangiocytes perform an essential role in important pathophysiologic functions the liver. Establishment of a human cholangiocyte line facilitates advances research and clinical applications for cell therapies. Here, we describe immortalization cholangiocytes using serial transfection simian virus 40 large T (SV40T) followed by telomerase reverse transcriptase (hTERT). Methods. SV40T-transduced liver OUMS-21 cells were superinfected with retroviral vector SSR#197 encoding hTERT...
Accumulating evidence indicates that dysfunction of mitochondria is a common feature Parkinson disease. Functional loss familial disease-linked gene, BRPK/PINK1 (PINK1), results in deterioration mitochondrial functions and eventual neuronal cell death. A chaperone protein has been shown to be substrate PINK1 kinase activity. In this study, we demonstrated another action point the cytoplasm. Phosphorylation Akt at Ser-473 was enhanced by overexpression PINK1, activation crucial for protection...
Abstract S100A8 and S100A9 are known to be up‐regulated in hyperproliferative psoriatic epidermis, but their function epidermal keratinocytes remains largely unknown. Here we show that (1) secreted by cultured normal human (NHK) a cytokine‐dependent manner, (2) when applied NHK, recombinant S100A8/A9 (a 1:1 mixture of S100A9) induced expression number cytokine genes such as IL‐8/CXCL8, CXCL1, CXCL2, CXCL3, CCL20, IL‐6, TNFα (3) the S100A8/A9‐induced cytokines turn enhanced production...
Mutations in PTEN-induced putative kinase 1 (PINK1) or parkin cause autosomal recessive forms of Parkinson's disease. Recent work suggests that loss mitochondrial membrane potential stabilizes PINK1 and accumulated recruits from the cytoplasm to mitochondria for elimination depolarized mitochondria, which is known as mitophagy. In this study, we find a complex with sterile α TIR motif containing (SARM1) tumor necrosis factor receptor–associated 6 (TRAF6), important import outer stabilization...
Human epidermal growth factor receptor 2 (HER2) is a member of the HER family proteins containing four tyrosine kinases. It plays an important role in pathogenesis certain human cancers. In non-small-cell lung cancer (NSCLC), HER2 amplification or mutations have been reported. However, little known about benefit HER2-targeted therapy for NSCLCs harboring alterations. this study, we investigated antitumor effect afatinib, irreversible (EGFR)-HER2 dual inhibitor, cancers oncogene alterations,...
Sepsis is a major cause of death worldwide. We show that plasma protein histidine-rich glycoprotein (HRG) was decreased significantly in septic mice with cecal ligation and puncture (CLP) supplementary treatment exogenous HRG improved survival, strong inhibition tight attachment neutrophils to pulmonary vasculatures, subsequent immunothrombosis, DIC state, lung inflammation, hypercytokinemia, activation vascular endothelial cells (VECs). In contrast, knockdown by siRNA exacerbated lethality....
An increase in extracellular Ca2+ induces growth arrest and differentiation of human keratinocytes culture. We examined possible involvement S100C/A11 this regulation. On exposure the cells to high Ca2+, was specifically phosphorylated at 10Thr 94Ser. Phosphorylation facilitated binding nucleolin, resulting nuclear translocation S100C/A11. In nuclei, liberated Sp1/3 from nucleolin. The free transcriptionally activated p21CIP1/WAF1, a representative negative regulator cell growth....
We examined the expression of REIC/Dkk-3, a possible candidate for tumor suppressor gene, in human renal clear cell carcinoma (RCCC) lines and sporadic RCCC surgical specimens.Human (Caki-1, Caki-2, ACHN KPK-1) several control were used to examine REIC/Dkk-3 mRNA characterize newly raised antibody specific protein. Pairs cancerous adjacent noncancerous tissues obtained from 20 patients with RCCC. Of them 17 7 cases analyzed by real-time quantitative reverse transcriptase-polymerase chain...
Many lines of evidence indicate that neoplastic transformation cells occurs by a multistep process. For normal human cells, they must be first immortalized and then converted into cells. It is well known the immortalization critical step for immortal phenotype recessive. Thus, we investigated proteins downregulated in two-dimensional gel electrophoresis. As result, S100C, Ca(2+)-binding protein, was dramatically fibroblasts compared with their counterparts. When reached confluence, S100C...
Abstract REIC/Dickkopf-3 (Dkk-3), a tumor suppressor gene, has been investigated in gene therapy studies. Our previous study suggested that REIC/Dkk-3–induced apoptosis mainly resulted from phosphorylation of c-Jun-NH2 kinase (JNK) prostate cancer cells. However, the precise mechanisms, especially molecular mechanisms regulating JNK phosphorylation, remain unclear. In this study, we participating context refractory disease, malignant mesothelioma (MM). Adenovirus-mediated overexpression...