- Antimicrobial Peptides and Activities
- Immune Response and Inflammation
- Virus-based gene therapy research
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Helicobacter pylori-related gastroenterology studies
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Telomeres, Telomerase, and Senescence
- Tea Polyphenols and Effects
- Neuropeptides and Animal Physiology
- Advanced Glycation End Products research
- Neurogenesis and neuroplasticity mechanisms
- Calpain Protease Function and Regulation
- Gastric Cancer Management and Outcomes
- Phytochemistry and biological activity of medicinal plants
- Polymer composites and self-healing
- Inflammasome and immune disorders
- Biochemical and Structural Characterization
- Calcium signaling and nucleotide metabolism
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Showa University Fujigaoka Hospital
2023
Juntendo University
2010-2022
Yokohama City University
1999-2021
RIKEN Center for Integrative Medical Sciences
2021
Tokyo University of Pharmacy and Life Sciences
2019-2020
Tohoku University
2009-2017
Meiji University
2017
Kyorin University
2014-2016
Hokkaido University
2016
Chiba University
2015
Oncolytic adenoviruses are promising therapies for the treatment of gliomas. However, untargeted viral replication and paucity coxsackie-adenovirus receptors (CARs) on tumor cells major stumbling blocks adenovirus-based treatment. We studied antiglioma activity tumor-selective Delta-24 adenovirus, which encompasses an early 1 A adenoviral (E1A) deletion in retinoblastoma (Rb) protein-binding region, Delta-24-RGD adenovirus. has RGD-4C peptide motif inserted into fiber, allows adenovirus to...
Intestinal metaplasia of the human stomach was classified into two types, complete and incomplete. The type associated with intestinal marker enzymes sucrose alpha-D-glucohydrolase, alpha, alpha-trehalase, aminopeptidase (microsomal) (APM), alkaline phosphatase (ALP). Tissue this contained goblet cells Paneth's but not high-iron diamine (HID)-positive mucin staining HID-Alcian blue. incomplete APM, cells, HID-positive ALP, or cells. For examination distribution types in 84, 27, 16 resected...
The molecular signaling pathways orchestrating the biology of cancer stem-like cells (CSLCs), including glioblastoma, remain to be elucidated. We investigated in this study role MEK/extracellular signal-regulated kinase (ERK) pathway control self-renewal and tumorigenicity glioblastoma CSLCs, particularly relation PI3K/mTOR (mammalian target rapamycin) pathway. Targeted inactivation MEK alone using pharmacological inhibitors or siRNAs resulted reduced sphere formation both cell line-...
Pyroptosis is a caspase-1 dependent cell death, associated with proinflammatory cytokine production, and considered to play crucial role in sepsis. induced by the two distinct stimuli, microbial PAMPs (pathogen molecular patterns) endogenous DAMPs (damage patterns). Importantly, cathelicidin-related AMPs (antimicrobial peptides) have innate immune defense. Notably, human cathelicidin LL-37 exhibits protective effect on septic animal models. Thus, this study, elucidate mechanism for action of...
Oncolytic viruses that are replication competent in tumor but not normal cells represent a novel approach for treating neoplastic diseases. However, the oncolytic potency of replicating agents is determined directly by their capability infecting target cells. Most adenoviruses used gene therapy or virotherapy have been based on serotype 5 (Ad5). Unfortunately, expression primary receptor Ad5 (the coxsackie–adenovirus receptor, CAR) highly variable ovarian and other cancer By performing...
Abstract Overcoming the resistance of glioblastoma cells against temozolomide, first-line chemotherapeutic agent choice for newly diagnosed glioblastoma, is a major therapeutic challenge in management this deadly brain tumor. The gene encoding O6-methylguanine DNA methyltransferase (MGMT), which removes methyl group attached by often silenced promoter methylation but nevertheless expressed significant fraction cases and therefore regarded as one most clinically relevant mechanisms...
Glioblastoma, the most intractable cerebral tumor, is highly lethal. Recent studies suggest that cancer stem-like cells (CSLCs) have capacity to repopulate tumors and mediate radio- chemoresistance, implying future therapies may need turn from elimination of rapidly dividing, but differentiated, tumor specifically targeting minority tumor. However, mechanism by which glioblastoma CSLCs maintain their immature state or, alternatively, become committed differentiation poorly understood. Here,...
Abstract LL-37 is the only known member of cathelicidin family antimicrobial peptides in humans. In addition to its broad spectrum activities, can modulate various inflammatory reactions. We previously revealed that suppresses LPS/ATP-induced pyroptosis macrophages vitro by both neutralizing action LPS and inhibiting response P2X7 (a nucleotide receptor) ATP. Thus, this study, we further evaluated effect on vivo using a cecal ligation puncture (CLP) sepsis model. As result, intravenous...
Sepsis is a systemic disease resulting from harmful host response to bacterial infections. During the exacerbation of severe sepsis or septic shock, apoptosis endothelial cells induced in susceptible organs such as lung and liver triggers microcirculatory disorder organ dysfunction. LPS, an outer membrane component Gram-negative bacteria, one major virulence factors for pathogenesis. We previously reported that LL-37, human anti-microbial cathelicidin peptide, potently neutralizes biological...
Helicobacter pylori strains produce tumor necrosis factor-α (TNF-α)-inducing protein, Tipα as a carcinogenic factor in the gastric epithelium. acts homodimer with 38-kDa whereas del-Tipα is an inactive monomer. H. isolated from cancer patients secreted large amounts of Tipα, which are incorporated into cells by directly binding to nucleolin on cell surface, receptor Tipα. The complex induces expression TNF-α and chemokine genes, activates NF-κB (nuclear kappa-light-chain-enhancer activated B...
purpose. The corneal endothelium is a target of the aging process. This study was undertaken to reveal relationship between endothelial cell (CEC) death and accumulation advanced glycation end products (AGEs), by investigating possible mechanism AGE in CECs its effects on CEC death. methods. First, vivo expression receptor investigated for (RAGE) galectin-3, both receptors AGE, at mRNA protein levels. Second, AGEs were added culture media cultured CECs, uptake AGEs, generation reactive...
To more clearly understand the molecular mechanisms involved in synergistic enhancement of cancer preventive activity with green tea polyphenol (-)-epigallocatechin gallate (EGCG), we examined effects cotreatment EGCG plus celecoxib, a cyclooxygenase-2 selective inhibitor. We specifically looked for induction apoptosis and expression related genes, emphasis on growth arrest DNA damage-inducible 153 (GADD153) gene, human lung cell line PC-9: Cotreatment celecoxib strongly induced both GADD153...
Peptide antibiotics possess the potent antimicrobial activities against invading microorganisms and contribute to innate host defense. Human peptides, α-defensins (human neutrophil HNPs), human β-defensins (hBDs), cathelicidin (LL-37) not only exhibit bactericidal Gram-negative Gram-positive bacteria, but also function as immunomodulatory molecules by inducing cytokine chemokine production, inflammatory immune cell activation. Neutrophil is a critical effector in defense microbial infection,...
Abstract The liver is a major organ that removes waste substances from the blood, and sinusoidal endothelial cells (LSECs) are professional scavenger cells, which incorporate degrade various endogenous exogenous molecules including pathogenic factor LPS. Mammalian express number of peptide antibiotics function as effectors in innate host defense systems. LL-37, human cathelicidin antimicrobial peptide, has potent LPS-neutralizing activity exhibits protective actions on infection models....
Abstract A mutant form of epidermal growth factor receptor ( EGFR ), v III , is common in glioblastoma GBM ) and confers enhanced tumorigenic activity drug resistance. Nimotuzumab, an anti‐ antibody, has shown preclinical clinical to but its specific against not been fully investigated. Human glioma U87 MG or LNZ 308 cells overexpressing either wild‐type (wt) were treated with nimotuzumab, temozolomide, both. Expression phosphorylation status molecules determined by Western blot analysis....
Purpose. The purpose of this study was to evaluate the effect advanced glycation end products (AGEs) in Descemet's membrane on attachment and spreading corneal endothelial cells. Methods. An anti-AGEs monoclonal antibody (6D12), which recognizes a N e -carboxymethyl lysine (CML)-protein adduct as an epitope, used for immunohistochemistry enzyme-linked immunosorbent assay (ELISA). Fresh bovine incubated 4 weeks buffered solution with 500 mM glucose-6-phosphate (G-6-P). In membrane,...
LL‑37 is the sole antimicrobial peptide of human cathelicidin comprising 37 amino acids, which expressed mainly in epithelial cells and neutrophils, activates mast cells. In present study, order to elucidate mechanism cell activation by LL‑37, associations between internalization Mas‑related gene X2 (MrgX2)‑mediated (degranulation) was investigated using line, LAD2. rapidly internalized into cells, induced degranulation, as assessed extracellular release β‑hexosaminidase. Pertussis toxin, a...