JP6057408B2 - 癌の予防剤および/または治療剤 - Google Patents
癌の予防剤および/または治療剤 Download PDFInfo
- Publication number
- JP6057408B2 JP6057408B2 JP2012048422A JP2012048422A JP6057408B2 JP 6057408 B2 JP6057408 B2 JP 6057408B2 JP 2012048422 A JP2012048422 A JP 2012048422A JP 2012048422 A JP2012048422 A JP 2012048422A JP 6057408 B2 JP6057408 B2 JP 6057408B2
- Authority
- JP
- Japan
- Prior art keywords
- fir
- sap155
- firδexon2
- myc
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 206010028980 Neoplasm Diseases 0.000 title description 95
- 201000011510 cancer Diseases 0.000 title description 72
- 239000003814 drug Substances 0.000 title description 27
- 229940124597 therapeutic agent Drugs 0.000 title description 26
- 230000003449 preventive effect Effects 0.000 title description 12
- 239000003112 inhibitor Substances 0.000 claims description 53
- 239000000126 substance Substances 0.000 claims description 36
- 150000001875 compounds Chemical class 0.000 claims description 14
- 102100033008 Poly(U)-binding-splicing factor PUF60 Human genes 0.000 description 274
- 108010004107 poly-U binding splicing factor 60KDa Proteins 0.000 description 259
- 101000707567 Homo sapiens Splicing factor 3B subunit 1 Proteins 0.000 description 189
- 102100031711 Splicing factor 3B subunit 1 Human genes 0.000 description 189
- 210000004027 cell Anatomy 0.000 description 117
- 230000014509 gene expression Effects 0.000 description 113
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 81
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 81
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 81
- 108090000623 proteins and genes Proteins 0.000 description 79
- 102000004169 proteins and genes Human genes 0.000 description 64
- 108020004999 messenger RNA Proteins 0.000 description 55
- 108020004459 Small interfering RNA Proteins 0.000 description 54
- 210000001519 tissue Anatomy 0.000 description 51
- 101000836101 Homo sapiens Histone deacetylase complex subunit SAP130 Proteins 0.000 description 32
- 101000616172 Homo sapiens Splicing factor 3B subunit 3 Proteins 0.000 description 32
- 102100021816 Splicing factor 3B subunit 3 Human genes 0.000 description 32
- 230000006870 function Effects 0.000 description 27
- 108700024542 myc Genes Proteins 0.000 description 26
- 238000013518 transcription Methods 0.000 description 25
- 230000035897 transcription Effects 0.000 description 25
- 238000000034 method Methods 0.000 description 23
- 206010009944 Colon cancer Diseases 0.000 description 22
- 238000001413 far-infrared spectroscopy Methods 0.000 description 22
- 108010087705 Proto-Oncogene Proteins c-myc Proteins 0.000 description 21
- 102000009092 Proto-Oncogene Proteins c-myc Human genes 0.000 description 21
- 150000001413 amino acids Chemical class 0.000 description 21
- 239000002299 complementary DNA Substances 0.000 description 21
- 239000013598 vector Substances 0.000 description 21
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 238000001262 western blot Methods 0.000 description 17
- 238000011529 RT qPCR Methods 0.000 description 16
- 101000707770 Homo sapiens Splicing factor 3B subunit 2 Proteins 0.000 description 14
- 102100031436 Splicing factor 3B subunit 2 Human genes 0.000 description 14
- 239000011324 bead Substances 0.000 description 14
- 239000000523 sample Substances 0.000 description 13
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 12
- 108020004414 DNA Proteins 0.000 description 12
- 241000282414 Homo sapiens Species 0.000 description 12
- 108091028690 C-myc mRNA Proteins 0.000 description 11
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 11
- 206010021042 Hypopharyngeal cancer Diseases 0.000 description 11
- 206010056305 Hypopharyngeal neoplasm Diseases 0.000 description 11
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 11
- 210000000981 epithelium Anatomy 0.000 description 11
- 201000004101 esophageal cancer Diseases 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 201000006866 hypopharynx cancer Diseases 0.000 description 11
- 230000000069 prophylactic effect Effects 0.000 description 11
- 230000004913 activation Effects 0.000 description 10
- 208000029742 colonic neoplasm Diseases 0.000 description 10
- 238000003757 reverse transcription PCR Methods 0.000 description 10
- 101001087352 Homo sapiens Poly(U)-binding-splicing factor PUF60 Proteins 0.000 description 9
- 230000003247 decreasing effect Effects 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 102000053602 DNA Human genes 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 230000002596 correlated effect Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 7
- 108091034117 Oligonucleotide Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 201000007270 liver cancer Diseases 0.000 description 7
- 208000014018 liver neoplasm Diseases 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 241000701161 unidentified adenovirus Species 0.000 description 7
- 102000007469 Actins Human genes 0.000 description 6
- 108010085238 Actins Proteins 0.000 description 6
- 101710120623 FERM, ARHGEF and pleckstrin domain-containing protein 2 Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000002337 electrophoretic mobility shift assay Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 230000002103 transcriptional effect Effects 0.000 description 6
- 101000575639 Homo sapiens Ribonucleoside-diphosphate reductase subunit M2 Proteins 0.000 description 5
- 206010061309 Neoplasm progression Diseases 0.000 description 5
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 5
- 102100026006 Ribonucleoside-diphosphate reductase subunit M2 Human genes 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000013604 expression vector Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000009368 gene silencing by RNA Effects 0.000 description 5
- 238000001114 immunoprecipitation Methods 0.000 description 5
- 230000006916 protein interaction Effects 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 230000005751 tumor progression Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 238000000692 Student's t-test Methods 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 210000002919 epithelial cell Anatomy 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 150000007523 nucleic acids Chemical group 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000012353 t test Methods 0.000 description 4
- 230000037426 transcriptional repression Effects 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 102000053642 Catalytic RNA Human genes 0.000 description 3
- 108090000994 Catalytic RNA Proteins 0.000 description 3
- 102100027100 Echinoderm microtubule-associated protein-like 4 Human genes 0.000 description 3
- 108700024394 Exon Proteins 0.000 description 3
- -1 FIRΔexon2 Proteins 0.000 description 3
- 101001057929 Homo sapiens Echinoderm microtubule-associated protein-like 4 Proteins 0.000 description 3
- 108010039259 RNA Splicing Factors Proteins 0.000 description 3
- 102000015097 RNA Splicing Factors Human genes 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 3
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 3
- 108091092562 ribozyme Proteins 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 108010031111 EBV-encoded nuclear antigen 1 Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101001028283 Homo sapiens FERM, ARHGEF and pleckstrin domain-containing protein 2 Proteins 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- 101150039798 MYC gene Proteins 0.000 description 2
- 102100025169 Max-binding protein MNT Human genes 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 229940079156 Proteasome inhibitor Drugs 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000012830 cancer therapeutic Substances 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000030570 cellular localization Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 102000043476 human FARP2 Human genes 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 238000003365 immunocytochemistry Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 108010005636 polypeptide C Proteins 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000003207 proteasome inhibitor Substances 0.000 description 2
- 239000003531 protein hydrolysate Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000001235 sensitizing effect Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 210000001324 spliceosome Anatomy 0.000 description 2
- 238000003153 stable transfection Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 108091006107 transcriptional repressors Proteins 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- OEPOKWHJYJXUGD-UHFFFAOYSA-N 2-(3-phenylmethoxyphenyl)-1,3-thiazole-4-carbaldehyde Chemical compound O=CC1=CSC(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=N1 OEPOKWHJYJXUGD-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 101710111216 Activated RNA polymerase II transcriptional coactivator p15 Proteins 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101710202081 FAD-linked sulfhydryl oxidase Proteins 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 102100032863 General transcription factor IIH subunit 3 Human genes 0.000 description 1
- 208000034951 Genetic Translocation Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101000666405 Homo sapiens General transcription factor IIH subunit 1 Proteins 0.000 description 1
- 101000655398 Homo sapiens General transcription factor IIH subunit 2 Proteins 0.000 description 1
- 101000655391 Homo sapiens General transcription factor IIH subunit 3 Proteins 0.000 description 1
- 101000655406 Homo sapiens General transcription factor IIH subunit 4 Proteins 0.000 description 1
- 101000655402 Homo sapiens General transcription factor IIH subunit 5 Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 101710150912 Myc protein Proteins 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 101710156990 Protein S100-A9 Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102100022154 Ragulator complex protein LAMTOR2 Human genes 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- CGNLCCVKSWNSDG-UHFFFAOYSA-N SYBR Green I Chemical compound CN(C)CCCN(CCC)C1=CC(C=C2N(C3=CC=CC=C3S2)C)=C2C=CC=CC2=[N+]1C1=CC=CC=C1 CGNLCCVKSWNSDG-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 102000004598 Small Nuclear Ribonucleoproteins Human genes 0.000 description 1
- 108010003165 Small Nuclear Ribonucleoproteins Proteins 0.000 description 1
- 241000251131 Sphyrna Species 0.000 description 1
- 208000000277 Splenic Neoplasms Diseases 0.000 description 1
- 102300035213 Splicing factor 3B subunit 1 isoform 1 Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 238000011053 TCID50 method Methods 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108010072724 U2 Small Nuclear Ribonucleoprotein Proteins 0.000 description 1
- 102000006986 U2 Small Nuclear Ribonucleoprotein Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 238000002170 nanoflow liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 238000000730 protein immunoprecipitation Methods 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000012755 real-time RT-PCR analysis Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 201000002471 spleen cancer Diseases 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000009495 transient activation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000001086 yeast two-hybrid system Methods 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012048422A JP6057408B2 (ja) | 2012-03-05 | 2012-03-05 | 癌の予防剤および/または治療剤 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012048422A JP6057408B2 (ja) | 2012-03-05 | 2012-03-05 | 癌の予防剤および/または治療剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013184887A JP2013184887A (ja) | 2013-09-19 |
| JP2013184887A5 JP2013184887A5 (enExample) | 2015-04-23 |
| JP6057408B2 true JP6057408B2 (ja) | 2017-01-11 |
Family
ID=49386650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012048422A Active JP6057408B2 (ja) | 2012-03-05 | 2012-03-05 | 癌の予防剤および/または治療剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6057408B2 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6304594B2 (ja) * | 2014-05-29 | 2018-04-04 | 国立大学法人千葉大学 | 芳香環含有化合物並びに癌の予防剤および/または治療剤 |
| ES2887201T3 (es) | 2015-09-01 | 2021-12-22 | Eisai R&D Man Co Ltd | Variantes de empalme asociadas con mutantes neomórficos de SF3B1 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2510087A2 (en) * | 2009-12-11 | 2012-10-17 | The Brigham and Women's Hospital, Inc. | Pathogen restriction factors |
| WO2011129427A1 (ja) * | 2010-04-16 | 2011-10-20 | 第一三共株式会社 | 癌の診断剤および治療剤 |
-
2012
- 2012-03-05 JP JP2012048422A patent/JP6057408B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013184887A (ja) | 2013-09-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6636067B2 (ja) | c−MAFを用いた前立腺がん転移の診断、予後診断および処置のための方法 | |
| JP2010536366A5 (enExample) | ||
| KR20100075857A (ko) | 폐암의 치료 및 진단의 표적유전자인 ebi3,dlx5,nptx1 및 cdkn | |
| JP2009540803A (ja) | 癌に関与するポリヌクレオチド配列およびポリペプチド配列 | |
| Matsushita et al. | SAP155-mediated splicing of FUSE-binding protein-interacting repressor serves as a molecular switch for c-myc gene expression | |
| EP2179286A2 (en) | Trim24 (tif1a) as p53 modulator and cancer target | |
| JP2017514514A (ja) | がんにおける融合遺伝子 | |
| Li et al. | Clusterin induced by N, N′-Dinitrosopiperazine is involved in nasopharyngeal carcinoma metastasis | |
| Hu et al. | Long noncoding RNA MIR210HG is induced by hypoxia-inducible factor 1α and promotes cervical cancer progression | |
| JP7249044B2 (ja) | 腫瘍細胞の悪性化抑制剤及び抗腫瘍剤 | |
| JP5515071B2 (ja) | 抗がん剤の作用増強剤及びその利用、並びにがん患者の予後推定用バイオマーカー及びその利用 | |
| WO2016152352A1 (ja) | メラノーマ特異的バイオマーカー及びその利用 | |
| JP5150855B2 (ja) | Cdca1−kntc2複合体を標的とするスクリーニングおよびnsclcの治療方法 | |
| KR20240156639A (ko) | 암 진단 및 prmt5 억제제에 의한 치료 | |
| JP6519927B2 (ja) | 癌の診断、阻害剤のスクリーニングにおけるrhoaの使用 | |
| US20110027297A1 (en) | Methods Involving MS4A12 and Agents Targeting MS4A12 for Therapy, Diagnosis and Testing | |
| JP2013184887A (ja) | 癌の予防剤および/または治療剤 | |
| Lei et al. | SerpinB5 interacts with KHDRBS3 and FBXO32 in gastric cancer cells | |
| Zhang et al. | E74-like factor 2 regulates valosin-containing protein expression | |
| WO2008044787A1 (fr) | Composition pour le traitement du cancer à l'aide de dref comme cible moléculaire | |
| US20240043557A1 (en) | A platform to obtain monoclonal antibodies directed against processed tumor-specific antigens | |
| US20110070245A1 (en) | Imp-1 oncogene as a therapeutic target and prognostic indicator for lung cancer | |
| CN101664550A (zh) | 治疗或预防癌症的方法和药物 | |
| JP7250307B2 (ja) | 子宮癌の発症、転移又は再発の予測方法 | |
| Sun et al. | CircNSD2 promotes metastasis and immune escape by increasing the USP10/SRSF6-mediated alternative splicing of TPM1 in TNBC |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150304 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150304 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160202 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160404 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160830 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161028 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20161122 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20161202 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6057408 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |