A5067674764- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Toxin Mechanisms and Immunotoxins
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Boron Compounds in Chemistry
- CRISPR and Genetic Engineering
- Nuclear Physics and Applications
- Cancer Research and Treatments
- Calcium signaling and nucleotide metabolism
- Cancer therapeutics and mechanisms
- Integrated Circuits and Semiconductor Failure Analysis
- Microtubule and mitosis dynamics
- Signaling Pathways in Disease
- Radiopharmaceutical Chemistry and Applications
- Radiation Therapy and Dosimetry
- Boron and Carbon Nanomaterials Research
- Nuclear Structure and Function
- Molecular Biology Techniques and Applications
- Plant Virus Research Studies
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- Pluripotent Stem Cells Research
Nagasaki University
2016-2025
Japan Radioisotope Association
2015-2024
Tokyo Women's Medical University
2022
NTL Institute for Applied Behavioral Science
2021
National Cancer Centre Japan
2010-2020
Chiba Cancer Center
2011-2016
National Cancer Research Institute
2001-2015
Weatherford College
2013
Centre Hospitalier de Beauvais
2013
Sumitomo Electric Industries (United States)
2013
Oxidative DNA damage causes blocks and errors in transcription replication, leading to cell death genomic instability. Although repair mechanisms of the have been extensively analyzed vitro , actual vivo processes remain largely unknown. Here, by irradiation with an UVA laser through a microscope lens, we conditionally produced single-strand breaks oxidative base at restricted nuclear regions mammalian cells. We showed, real time after using antibodies GFP-tagged proteins, rapid ordered...
Streptozotocin (STZ), a glucose analogue known to induce diabetes in experimental animals, causes DNA strand breaks and subsequent activation of poly(ADPribose) polymerase (Parp). Because Parp uses NAD as substrate, extensive damage will result reduction cellular level. In fact, STZ induces depletion cell death isolated pancreatic islets vitro . Activation therefore is thought play an important role STZ-induced diabetes. the present study, we established Parp-deficient ( −/− ) mice by...
Integration of a DNA copy the viral RNA genome is crucial step in life cycle human immunodeficiency virus type 1 (HIV-1) and other retroviruses. While virally encoded integrase key to this process, cellular factors yet be characterized are suspected participate its completion. damage sensors such as ATM (ataxia-telangiectasia mutated), ATR (ATM- Rad3-related), DNA-PK (DNA-dependent protein kinase), PARP-1 [poly(ADP-ribose) polymerase 1] play central roles responses various forms injury could...
Embryonic stem (ES) cells are in a dynamic equilibrium of distinct functional states, characterized by the heterogeneous expression critical pluripotency factors and regulated spectrum reversible histone modifications. Maintenance this is hallmark pluripotency. Here we find that ADP-ribosyltransferases Parp1 Parp7 play role safeguarding state occupying key genes, notably Nanog, Pou5f1, Sox2, Stella, Tet1 Zfp42, thereby protecting them from progressive epigenetic repression. In absence either...
Single-strand breaks (SSBs) are the most common type of oxidative DNA damage and they related to aging many genetic diseases. The scaffold protein for repair SSBs, XRCC1, accumulates at sites poly(ADP-ribose) (pAR) synthesized by PARP, but it is retained SSBs after pAR degradation. How XRCC1 responds degradation how this affects progression not well understood. We found that dissociates from translocated dependent on its BRCTII domain function PARG. In addition, phosphorylation also required...
Abstract The uterine bed undergoes remarkable changes during pregnancy, including proliferation and decidualization of the stroma remodeling angiogenesis maternal vasculature. Fetal‐derived trophoblast giant cells invade into uterus where they gain access to blood circulation ensure sufficient nutrient supply embryo. In serial sections through early‐ mid‐gestation conceptuses, we have determined exact distance invasion expression angiogenic, vasodilatory, anticoagulative factors that are...
Hematopoietic cytokines transduce cell survival signals, which are distinct from the signals necessary for stimulation of DNA synthesis. Recently, Ras and phosphatidylinositol 3-kinase pathways have been shown to play important roles in preventing apoptosis various types,e.g. hematopoietic cells neuronal cells. Withdrawal cytokine(s), turn, results rapid inactivation these eventually leads death accompanied by hallmarks apoptosis. However, mechanism caused cytokine deprivation has not fully...
Abstract Background Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation various genes as a coactivator or corepressor by modulating chromatin structure. However, the impact Parp-1 -deficiency on genome-wide gene expression has not been fully studied yet. Results We employed microarray analysis covering 12,488 and ESTs using mouse -deficient ( -/- ) embryonic stem (ES) cell livers mice their wild-type (Parp-1 +/+ counterparts....
Poly(ADP-ribose) glycohydrolase (PARG) is the primary enzyme responsible for degradation of poly(ADP-ribose). PARG dysfunction sensitizes cells to alkylating agents and induces cell death; however, details this effect have not been fully elucidated. Here, we investigated mechanism by which deficiency leads death in different types using methylmethanesulfonate (MMS), an agent, Parg−/− mouse ES human cancer lines. showed increased levels γ-H2AX, a marker DNA double strand breaks (DSBs),...
Poly( ADP ‐ribose) polymerase ( PARP )‐1 promotes base excision repair and DNA strand break repair. Inhibitors of enhance the cytotoxic effects γ‐irradiation X ‐irradiation. We investigated impact inhibition on responses to (low liner energy transfer [ LET ] radiation) carbon‐ion irradiation (high in human pancreatic cancer cell line MIA P a C a‐2. Cell survival was assessed by colony formation assay after combination treatment with inhibitor AZD 2281 single fraction (13 70 keV/μm 13 70])....
Abstract An accelerator-based boron neutron capture therapy (BNCT) system employing a solid-state Li target can achieve sufficient flux for treatment although the is reduced over lifetime of its target. In this study, reduction was examined in five targets, and model then established to represent flux. each target, observed based on integrated proton charge reached 28% after 2.52 × 10 6 mC delivered system. The calculated acquired by compared measured an charge, mean discrepancies were less...
Base excision repair (BER) removes damaged bases by generating single-strand breaks (SSBs), gap-filling DNA polymerase β (POLβ), and resealing SSBs. A base-damaging agent, methyl methanesulfonate (MMS) is widely used to study BER. BER increases cellular tolerance MMS, anti-cancer drugs, temozolomide, carmustine, lomustine, clinical poly(ADP ribose)polymerase (PARP) poisons, olaparib talazoparib. The poisons stabilize PARP1/SSB complexes, inhibiting access of factors PARP1 XRCC1...
Abstract Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of flux over lifetime target, and its could represent model. This study proposes novel compensatory approach for delivering required fluence validates clinical applicability. The proposed relies on model cumulative sum real-time measurements proton charges. accuracy BNCT using was examined in five Li targets. With approach, be delivered within 3.0%, 1.0% most...