Naoyuki Nishiya

Naoyuki Nishiya
Iwate Medical University · Department of Integrated Information for Pharmaceutical Sciences

PhD

About

38
Publications
3,182
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,798
Citations
Additional affiliations
June 2016 - December 2017
Iwate Medical University
Position
  • Professor

Publications

Publications (38)
Article
Full-text available
The aim of this study was to investigate the effect of the COVID-19 pandemic on regular clinic visits among people with diabetes and to elucidate the factors related to visit patterns among these patients during the pandemic. This was a longitudinal study using anonymized insurance claims data from the Joint Health Insurance Society in Tokyo from O...
Article
Full-text available
Ivermectin (IVM), an avermectin-derivative anthelmintic, specifically binds to glutamate-gated chloride ion channels (GluCls), causing paralysis in invertebrates. IVM also exhibits other biological activities such as Wnt/β-catenin pathway inhibition in vertebrates that do not possess GluCls. This study showed that affinity purification using immobi...
Article
Soil microorganisms are rich sources of bioactive natural products. Interspecies interactions are the cues of their production and refine biological activities. These interactions in natural environments include the interplay between microorganisms and Metazoans (animals), such as nematodes, insects, and ticks. Chemical intercellular communication...
Article
Background/aim: Tacrolimus is an essential immunosuppressant for successful allogeneic haematopoietic stem cell transplantation (Allo-HSCT). This study aimed to examine the change in the blood concentration of tacrolimus during switching from intravenous to oral administration in allo-HSCT for paediatric cancer to predict the optimal dosage. Pati...
Article
Full-text available
The emergence of acquired resistance is a major concern associated with molecularly targeted kinase inhibitors. The C797S mutation in the epidermal growth factor receptor (EGFR) confers resistance to osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI). We report that the derivatization of the marine alkaloid topoisomerase inhi...
Article
Azalamellarin N, a synthetic lactam congener of the marine natural product lamellarin N, and its A-ring-modified analogues were synthesized and evaluated as potent and non-covalent inhibitors of the drug-resistant epidermal growth factor receptor T790M/L858R mutant. An in vitro tyrosine kinase assay indicated that the inhibitory activities of the s...
Article
Aberrant activation of the canonical Wnt/β-catenin signaling pathway triggers tumorigenesis in various tissues. This study identified an atrarate compound, IMU14, derived from filamentous fungi as an inhibitor of Wnt/β-catenin signaling in phenotypic chemical inhibitor screening of the zebrafish eyeless phenotype. Its derivatization resulted in syn...
Article
Full-text available
Molecular targeting therapies often cause characteristic adverse effects, such as skin rash during anti-epidermal growth factor receptor (EGFR) therapies, making treatment continuation difficult. In contrast, skin symptoms induced by EGFR inhibition are strongly correlated with the overall survival of the therapies. Therefore, controlling adverse e...
Article
The Wnt/β-catenin signaling pathway controls cell proliferation and differentiation, and therefore, when this pathway is excessively activated, it causes tumorigenesis. Our chemical suppressor screening in zebrafish embryos identified antifungal azoles including clotrimazole, miconazole, and itraconazole, as Wnt/β-catenin signaling inhibitors. Here...
Article
Background: Transcriptional co-activators YES-associated protein (YAP) and transcriptional coactivator with PDZ-motif (TAZ) stimulate the expression of cell cycle-related genes to permit for tumour cell growth. MLN8237 is a potent aurora-A kinase inhibitor; however, patients responding to MLN8237 are limited. Therefore, rational combination therap...
Data
Fig. S1. YAP depletion sensitised OVCAR‐8 cells to AZD1775–olaparib. Fig. S2. Dasatinib sensitised OVCAR‐8 cells to AZD1775–olaparib.
Article
Full-text available
The main reasons for failure of cancer chemotherapy are intrinsic and acquired drug resistance. The Hippo pathway effector YAP is associated with resistance to both cytotoxic and molecular‐targeted drugs. Several lines of evidence indicate that YAP activates transcriptional programs to promote cell cycle progression and DNA damage responses. Theref...
Article
A series of A-ring-modified lamellarin N analogues were designed, synthesized, and evaluated as potential noncovalent inhibitors of the EGFR T790M/L858R mutant, a causal factor in the drug-resistant non-small cell lung cancer. Several water-soluble ammonium- or guanidinium-tethered analogues exhibited good kinase inhibitory activities. The most pro...
Article
Background: Breast tumor heterogeneity leads to phenotypic diversity, such as tumor-initiating and metastatic properties and drug sensitivity. Materials and methods: We found that a self-floating cell (SFC) culture enriches a drug-resistant subpopulation in a HER2-positive breast cancer cell line. SFCs were analyzed for cancer stem cell markers,...
Article
Aberrant activation of Wnt/β-catenin canonical signaling is observed in multiple malignant tumors, and is recognized as an attractive therapeutic target for molecular targeted drugs. This signaling pathway is also involved in maintaining pluripotency in adult stem cells. Therefore, lowering potential stem cell toxicity is a key factor for the devel...
Article
Full-text available
Aim: To identify non-quinazoline kinase inhibitors effective against drug resistant mutants of epidermal growth factor receptor (EGFR). Methods: A kinase inhibitor library was subjected to screening for specific inhibition pertaining to the in vitro kinase activation of EGFR with the gatekeeper mutation T790M, which is resistant to small molecul...
Article
Full-text available
YAP and TAZ oncoproteins confer malignancy and drug resistance to various cancer types. We screened for small molecules that inhibit the nuclear localization of YAP/TAZ. Dasatinib, statins and pazopanib inhibited the nuclear localization and target gene expression of YAP and TAZ. All three drugs induced phosphorylation of YAP and TAZ, and pazopanib...
Article
Genetic screening for suppressor mutants has been successfully used to identify important signaling regulators. Using an analogy to genetic suppressor screening, we developed a chemical suppressor screening method to identify inhibitors of the Wnt/β-catenin signaling pathway. We used zebrafish embryos in which chemically induced β-catenin accumulat...
Article
Full-text available
Accurate chromosome segregation is vital for cell viability. Many cancer cells show chromosome instability (CIN) due to aberrant expression of the genes involved in chromosome segregation. The induction of massive chromosome segregation errors in such cancer cells by small molecule inhibitors is an emerging strategy to kill these cells selectively....
Article
Candida albicans is the most common and virulent fungus causing candidiasis in various parts of the body and can be lethal to immunocompromised patients. All currently known antifungal therapies are drugs which cause serious side effects in the host. An inhibitor specific for fungus survival is an ideal therapeutic. C. albicans MPS1 (monopolar spin...
Article
Full-text available
Slit-Roundabout (Robo) signalling has a well-understood role in axon guidance. Unlike in the nervous system, however, Slit-dependent activation of an endothelial-specific Robo, Robo4, does not initiate a guidance program. Instead, Robo4 maintains the barrier function of the mature vascular network by inhibiting neovascular tuft formation and endoth...
Article
Full-text available
The angiogenic sprout has been compared to the growing axon, and indeed, many proteins direct pathfinding by both structures. The Roundabout (Robo) proteins are guidance receptors with well-established functions in the nervous system; however, their role in the mammalian vasculature remains ill defined. Here we show that an endothelial-specific Rob...
Article
Full-text available
The Wnt/β-catenin signaling pathway regulates cell fate and behavior during embryogenesis, adult tissue homeostasis, and regeneration. When inappropriately activated, the pathway has been linked to colorectal cancer and melanoma, and when attenuated it may contribute to Alzheimer's disease and osteoporosis. Small molecules that modulate Wnt signali...
Article
Formation of a stable lamellipodium at the front of migrating cells requires localization of Rac activation to the leading edge. Restriction of alpha4 integrin phosphorylation to the leading edge limits the interaction of alpha4 with paxillin to the sides and rear of a migrating cell. The alpha4-paxillin complex inhibits stable lamellipodia, thus c...
Article
Full-text available
Integrins regulate cellular behaviors through signaling pathways, including Rho GTPases and kinases. CD98 heterodimers, comprised of a heavy chain (CD98hc, SLC3A2) and one of several light chains, interact with integrins through CD98hc. CD98hc overexpression leads to anchorage-independent cell growth and tumorigenesis in 3T3 fibroblasts and activat...
Article
Hic-5, a member of the paxillin family of adaptor molecules, is localized at focal adhesion and implicated in integrin-mediated signaling. Hic-5 and paxillin exhibit structural homology and share interacting factors, however, diverse functions are suggested for them. In this study, we carried out yeast two-hybrid screening to identify Hic-5 interac...
Article
Full-text available
Hic-5 is a paxillin homologue that is localized to focal adhesion complexes. Hic-5 and paxillin share structural homology and interacting factors such as focal adhesion kinase (FAK), Pyk2/CAKβ/RAFTK, and PTP-PEST. Here, we showed that Hic-5 inhibits integrin-mediated cell spreading on fibronectin in a competitive manner with paxillin in NIH 3T3 cel...
Article
Full-text available
The Hic-5 protein is encoded by a transforming growth factor-β1- and hydrogen peroxide-inducible gene,hic-5, and has striking similarity to paxillin, especially in their C-terminal LIM domains. Like paxillin, Hic-5 is localized in focal adhesion plaques in association with focal adhesion kinase in cultured fibroblasts. We carried out yeast two-hybr...
Article
Full-text available
hic-5 protein is a member of the LIM protein family, containing four LIM domains in its C-terminal region. It is mainly localized in focal adhesions and shows striking similarity to paxillin in its LIM domains, although the function of these LIM domains has remained elusive. In the present study, we found that full-length and the C-terminal half of...
Article
Full-text available
The hic-5 gene encodes a novel protein with Zn finger-like (LIM) motifs, the expression of which increases during cellular senescence. The ectopic expression of hic-5 in nontumorigenic immortalized human fibroblasts, whose expression levels of hic-5 were significantly reduced in comparison with those of mortal cells, decreased colony-forming effici...

Network

Cited By