JP6895175B2 - エクソソーム分泌阻害剤 - Google Patents
エクソソーム分泌阻害剤 Download PDFInfo
- Publication number
- JP6895175B2 JP6895175B2 JP2017539125A JP2017539125A JP6895175B2 JP 6895175 B2 JP6895175 B2 JP 6895175B2 JP 2017539125 A JP2017539125 A JP 2017539125A JP 2017539125 A JP2017539125 A JP 2017539125A JP 6895175 B2 JP6895175 B2 JP 6895175B2
- Authority
- JP
- Japan
- Prior art keywords
- gene
- substance
- expression
- exosomes
- cancer
- 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
- 210000001808 exosome Anatomy 0.000 title claims description 114
- 230000028327 secretion Effects 0.000 title claims description 53
- 239000003112 inhibitor Substances 0.000 title claims description 16
- 108090000623 proteins and genes Proteins 0.000 claims description 111
- 210000004027 cell Anatomy 0.000 claims description 104
- 239000000126 substance Substances 0.000 claims description 98
- 108020004459 Small interfering RNA Proteins 0.000 claims description 62
- 230000014509 gene expression Effects 0.000 claims description 53
- 206010028980 Neoplasm Diseases 0.000 claims description 51
- 201000011510 cancer Diseases 0.000 claims description 46
- 238000000034 method Methods 0.000 claims description 42
- 239000002679 microRNA Substances 0.000 claims description 41
- 238000012360 testing method Methods 0.000 claims description 40
- 108091070501 miRNA Proteins 0.000 claims description 39
- 102100030916 Gamma-soluble NSF attachment protein Human genes 0.000 claims description 37
- 102000004169 proteins and genes Human genes 0.000 claims description 34
- 102100025291 Adenosine 5'-monophosphoramidase HINT3 Human genes 0.000 claims description 32
- 101000702693 Homo sapiens Gamma-soluble NSF attachment protein Proteins 0.000 claims description 32
- 230000000694 effects Effects 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 101150007366 Gxylt1 gene Proteins 0.000 claims description 27
- 101150103861 HINT3 gene Proteins 0.000 claims description 27
- 101150003987 napG gene Proteins 0.000 claims description 26
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 21
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 21
- 206010027476 Metastases Diseases 0.000 claims description 20
- 230000009401 metastasis Effects 0.000 claims description 20
- 108091054642 miR-194 stem-loop Proteins 0.000 claims description 19
- 101001006021 Homo sapiens Adenosine 5'-monophosphoramidase HINT3 Proteins 0.000 claims description 17
- 101000906417 Homo sapiens Glucoside xylosyltransferase 1 Proteins 0.000 claims description 17
- 239000013604 expression vector Substances 0.000 claims description 17
- 230000002401 inhibitory effect Effects 0.000 claims description 17
- 102100023525 Glucoside xylosyltransferase 1 Human genes 0.000 claims description 16
- 108091034117 Oligonucleotide Proteins 0.000 claims description 15
- 108090000994 Catalytic RNA Proteins 0.000 claims description 14
- 102000053642 Catalytic RNA Human genes 0.000 claims description 14
- 108091092562 ribozyme Proteins 0.000 claims description 14
- 238000012216 screening Methods 0.000 claims description 13
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 7
- 239000002924 silencing RNA Substances 0.000 claims description 7
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 32
- 235000018102 proteins Nutrition 0.000 description 31
- 239000012228 culture supernatant Substances 0.000 description 24
- 102000039446 nucleic acids Human genes 0.000 description 22
- 108020004707 nucleic acids Proteins 0.000 description 22
- 150000007523 nucleic acids Chemical class 0.000 description 21
- 108020004999 messenger RNA Proteins 0.000 description 18
- 125000003275 alpha amino acid group Chemical group 0.000 description 15
- 230000035772 mutation Effects 0.000 description 15
- 238000010586 diagram Methods 0.000 description 12
- 241000282414 Homo sapiens Species 0.000 description 11
- 108091081021 Sense strand Proteins 0.000 description 11
- 239000002773 nucleotide Substances 0.000 description 11
- 125000003729 nucleotide group Chemical group 0.000 description 11
- 230000000692 anti-sense effect Effects 0.000 description 10
- 230000000295 complement effect Effects 0.000 description 10
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 9
- 239000002777 nucleoside Substances 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 239000002609 medium Substances 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 108700039582 histidine triad Proteins 0.000 description 7
- 102000050898 human NAPG Human genes 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 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 6
- 101100394038 Homo sapiens GXYLT1 gene Proteins 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 238000012815 AlphaLISA Methods 0.000 description 5
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 5
- 239000000090 biomarker Substances 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 125000003835 nucleoside group Chemical group 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 150000003384 small molecules Chemical class 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 239000012096 transfection reagent Substances 0.000 description 5
- 108020005544 Antisense RNA Proteins 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 4
- 108091093037 Peptide nucleic acid Proteins 0.000 description 4
- 102100039767 Ras-related protein Rab-27A Human genes 0.000 description 4
- 108091027967 Small hairpin RNA Proteins 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 239000003184 complementary RNA Substances 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000009437 off-target effect Effects 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 108010033990 rab27 GTP-Binding Proteins Proteins 0.000 description 4
- 239000004055 small Interfering RNA Substances 0.000 description 4
- 101100070655 Homo sapiens HINT3 gene Proteins 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100021461 Sphingomyelin phosphodiesterase 3 Human genes 0.000 description 3
- 101710201918 Sphingomyelin phosphodiesterase 3 Proteins 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- -1 morpholinon nucleic acids Chemical class 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 102100037904 CD9 antigen Human genes 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 description 2
- 108700011259 MicroRNAs Proteins 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 241000021375 Xenogenes Species 0.000 description 2
- 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 Chemical class 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 2
- 230000009471 action Effects 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000005549 deoxyribonucleoside Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 230000007332 vesicle formation Effects 0.000 description 2
- 108700026220 vif Genes Proteins 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NJYXSKVOTDPOAT-LMVFSUKVSA-N (2r,3r,4r)-2-fluoro-3,4,5-trihydroxypentanal Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](F)C=O NJYXSKVOTDPOAT-LMVFSUKVSA-N 0.000 description 1
- QVNQIPRKTGHDRG-GJMOJQLCSA-N (2r,3r,4r)-3,4,5-trihydroxy-2-propoxypentanal Chemical compound CCCO[C@@H](C=O)[C@H](O)[C@H](O)CO QVNQIPRKTGHDRG-GJMOJQLCSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- STGXGJRRAJKJRG-JDJSBBGDSA-N (3r,4r,5r)-5-(hydroxymethyl)-3-methoxyoxolane-2,4-diol Chemical compound CO[C@H]1C(O)O[C@H](CO)[C@H]1O STGXGJRRAJKJRG-JDJSBBGDSA-N 0.000 description 1
- MXHRCPNRJAMMIM-ULQXZJNLSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidine-2,4-dione Chemical compound O=C1NC(=O)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 MXHRCPNRJAMMIM-ULQXZJNLSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- UZGKAASZIMOAMU-UHFFFAOYSA-N 124177-85-1 Chemical compound NP(=O)=O UZGKAASZIMOAMU-UHFFFAOYSA-N 0.000 description 1
- OTDJAMXESTUWLO-UUOKFMHZSA-N 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-oxolanyl]-3H-purine-6-thione Chemical compound C12=NC(N)=NC(S)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OTDJAMXESTUWLO-UUOKFMHZSA-N 0.000 description 1
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 1
- NLLCDONDZDHLCI-UHFFFAOYSA-N 6-amino-5-hydroxy-1h-pyrimidin-2-one Chemical compound NC=1NC(=O)N=CC=1O NLLCDONDZDHLCI-UHFFFAOYSA-N 0.000 description 1
- CKOMXBHMKXXTNW-UHFFFAOYSA-N 6-methyladenine Chemical compound CNC1=NC=NC2=C1N=CN2 CKOMXBHMKXXTNW-UHFFFAOYSA-N 0.000 description 1
- 208000035657 Abasia Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102100032412 Basigin Human genes 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 102100025222 CD63 antigen Human genes 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102100032257 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 1
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 1
- 102000012804 EPCAM Human genes 0.000 description 1
- 101150084967 EPCAM gene Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000798441 Homo sapiens Basigin Proteins 0.000 description 1
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 description 1
- 101100421764 Homo sapiens NAPG gene Proteins 0.000 description 1
- 101000744536 Homo sapiens Ras-related protein Rab-27B Proteins 0.000 description 1
- 101000638204 Homo sapiens Transmembrane emp24 domain-containing protein 5 Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- WXJXBKBJAKPJRN-UHFFFAOYSA-N Methanephosphonothioic acid Chemical class CP(O)(O)=S WXJXBKBJAKPJRN-UHFFFAOYSA-N 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000711408 Murine respirovirus Species 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102100039765 Ras-related protein Rab-27B Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 241000710960 Sindbis virus Species 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 101150057140 TACSTD1 gene Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102100032105 Transmembrane emp24 domain-containing protein 5 Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 102100035071 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000003016 alphascreen Methods 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
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000002215 arabinonucleoside Substances 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000008568 cell cell communication Effects 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940105990 diglycerin Drugs 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002700 inhibitory effect on cancer Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- CPQCSJYYDADLCZ-UHFFFAOYSA-N n-methylhydroxylamine Chemical compound CNO CPQCSJYYDADLCZ-UHFFFAOYSA-N 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 235000006180 nutrition needs Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 210000005048 vimentin Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y204/00—Glycosyltransferases (2.4)
- C12Y204/02—Pentosyltransferases (2.4.2)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5076—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving cell organelles, e.g. Golgi complex, endoplasmic reticulum
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
- C12N2310/141—MicroRNAs, miRNAs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Plant Pathology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Virology (AREA)
- Oncology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
Description
〔1〕 NAPG、HINT3、若しくはGXYLT1遺伝子の発現を抑制する物質又はNAPG、HINT3、若しくはGXYLT1タンパク質の活性を抑制する物質を含有してなる、エクソソーム分泌阻害剤。
〔1〕 NAPG、HINT3、若しくはGXYLT1遺伝子の発現を抑制する物質又はNAPG、HINT3、若しくはGXYLT1タンパク質の活性を抑制する物質を含有してなる、医薬組成物。
〔3〕 miR-194を含有してなる、エクソソーム分泌阻害剤。
〔4〕 NAPG、HINT3、若しくはGXYLT1遺伝子の発現又はNAPG、HINT3、若しくはGXYLT1タンパク質の活性を指標とし、発現の抑制又は活性の抑制をする物質を候補化合物とする、エクソソーム分泌阻害用物質のスクリーニング方法。
(i) NAPG、HINT3若しくはGXYLT1遺伝子の発現を抑制する物質又はNAPG、HINT3若しくはGXYLT1タンパク質の活性を抑制する物質を投与する工程を有する、癌を治療する方法、
(ii)癌の治療に用いられる、NAPG、HINT3若しくはGXYLT1遺伝子の発現を抑制する物質又はNAPG、HINT3若しくはGXYLT1タンパク質の活性を抑制する物質、ならびに
(iii)癌の治療剤の調製における、NAPG、HINT3若しくはGXYLT1遺伝子の発現を抑制する物質又はNAPG、HINT3若しくはGXYLT1タンパク質の活性を抑制する物質の使用
を提供する。
上記「遺伝子の発現を抑制する物質」又は「タンパク質の活性を抑制する物質」については、上で説明したとおりである。また、「遺伝子の発現を抑制する物質」として、siRNAが用いられる場合、好ましいsiRNAについては上述したとおりである。
(a1)エクソソーム量の測定可能な細胞と被験物質とを接触させる工程
(b1)被験物質を接触させた細胞におけるエクソソーム量を測定し、該測定値を、被験物質を接触させない対照細胞におけるエクソソーム量と比較する工程
(c1)被験物質を接触させた細胞におけるエクソソーム量が、被験物質を接触させない対照細胞におけるエクソソーム量よりも低下している場合に、被験物質をエクソソーム分泌阻害用物質として選択する工程
(a2)エクソソーム量の測定可能な細胞と被験物質とを接触させる工程
(b2)被験物質を接触させた細胞におけるエクソソーム量を測定し、該測定値を、予め測定しておいた被験物質を接触させる前の前記細胞におけるエクソソーム量と比較する工程
(c2)被験物質を接触させた細胞におけるエクソソーム量が、被験物質を接触させる前のエクソソーム量よりも低下している場合に、被験物質をエクソソーム分泌阻害用物質として選択する工程
96well plateに血清入りの培地で各ウェルに1×104個のPC-3ML細胞(Xenogen社)又はMDA-MB-231D3H2LN細胞(Xenogen社)を播種した。翌日、培養上清をadvanced RPMI(aRPMI; 血清無添加、抗生剤無添加)に交換した(90μL/well)。
次いで、DharmaFECT1 Transfection Reagent(Thermo Scientific)をaRPMIで10μL/wellになるように希釈し、5分間常温でインキュベートし、90μL/wellになるようにaRPMIを加えた。当該溶液を、前記miRNAを注入したPCR plate 1wellあたり90μLを加え、30分間常温でインキュベートした。30分間常温でインキュベーション後、90μLをPC-3ML細胞又はMDA-MB-231D3H2LN細胞を播種した96well plateの各wellにそれぞれ添加した。翌日培養上清を除去し、新しいaRPMIを60μL加えた。さらに24時間後、培養上清10μLをエクソソーム分泌量の定量に用い、残りの培養上清を細胞数の定量に用いた。なお各定量は以下の方法に従って行った。
回収した培養上清を96 well white plateの各ウェルに10μLずつ加える。
ビオチン化抗CD9抗体(シオノギ製薬, Clone 12A12)、ビオチン化抗CD63抗体(シオノギ製薬, Clone 8A12)を、AlphaLISA Universal Buffer (PerkinElmer社)を用いて5nMに希釈し、一方、AlphaLISA Acceptor Beadsと結合している抗CD9抗体(シオノギ製薬, Clone 12A12)、抗CD63抗体(シオノギ製薬, Clone 8A12)を、AlphaLISA Universal Buffer (PerkinElmer社)を用いて50μg/mLに希釈する。
培養上清に、5nMビオチン化抗体と、50μg/mL AlphaLISA Acceptor Beadsと結合している抗体を10μLずつ加えて、37℃遮光条件下で1時間インキュベートする。
5mg/mL AlphaScreenストレプトアビジンドナービーズ(PerkinElmer社)をAlphaLISA Universal Bufferで62.5倍に希釈し、25μLずつ各ウェルに加え、TopSeal-Aをプレートに貼り、37℃遮光条件下で30分間インキュベートし、Enspireで蛍光強度を測定する。
回収した培養上清に、MTS溶液(Dojindo, Cell Counting Kit-8)を50μL/wellになるように加え、37℃で1時間インキュベーションし、細胞数の増殖を測定する。
6 well plateに血清入りの培地で各ウェルに1×104個のPC-3ML細胞又はMDA-MB-231D3H2LN細胞を播種した。翌日、培養上清をadvanced RPMI(aRPMI; 血清無添加、抗生剤無添加)に交換した(2mL/well)。
96 well plateに血清入りの培地で各ウェルに1×104個のPC-3ML細胞又はMDA-MB-231D3H2LN細胞を播種した。翌日、培養上清をadvanced RPMIに交換した(90μL/well)。
次いで、DharmaFECT1 Transfection ReagentをaRPMIで10μL/wellになるように希釈し、5分間常温でインキュベートし、90μL/wellになるようにaRPMIを加えた。当該溶液を、PCR plate 1wellあたり90μLを加え、30分間常温でインキュベートした。30分間常温でインキュベーション後、90μLをPC-3ML細胞又はMDA-MB-231D3H2LN細胞を播種した96well plateの各wellにそれぞれ添加した。翌日培養上清を除去し、新しいaRPMIを60μL加えた。さらに24時間後、培養上清10μLをエクソソーム分泌量の定量に用い、残りの培養上清を細胞数の定量に用いた。各定量は実施例1と同様に行った。
6well plateに血清入りの培地で各ウェルに5×105個のPC-3ML細胞又はMDA-MB-231D3H2LN細胞を播種した。翌日、培養上清をadvanced RPMIに交換した(2mL/well)。
次いで、DharmaFECT1 Transfection ReagentをaRPMIで200μL/wellになるように希釈し、5分常温でインキュベートし、各siRNAが入っているチューブに加えた。30分間常温でインキュベートした後、400μLを各細胞のwellに添加した。
実施例2でmir-194のターゲット遺伝子候補として見出した、HINT3、GXYLT1の遺伝子についても、実施例3と同様の解析を行った。
具体的には、96 well plateに血清入りの培地で各ウェルに1×104個のMDA-MB-231D3H2LN細胞を播種した。翌日、培養上清をadvanced RPMIに交換した(90μL/well)。
次いで、DharmaFECT1 Transfection ReagentをaRPMIで10μL/wellになるように希釈し、5分間常温でインキュベートし、90μL/wellになるようにaRPMIを加えた。当該溶液を、PCR plate 1wellあたり90μLを加え、30分間常温でインキュベートした。30分間常温でインキュベーション後、90μLをMDA-MB-231D3H2LN細胞を播種した96well plateの各wellにそれぞれ添加した。翌日培養上清を除去し、新しいaRPMIを60μL加えた。さらに24時間後、培養上清10μLをエクソソーム分泌量の定量に用い、残りの培養上清を細胞数の定量に用いた。各定量は実施例1と同様に行った。
スキッドマウスの乳腺にMDA-MB-231D3H2LN細胞を1x106 cells/mouseで移植(各群10匹)した。移植1週間後から週2回、NAPGに対するsiRNAおよび陰性対照となるsiRNA(AllStars、キアゲン社)を20μg/mouse、in vivo-jetPEI(Polyplus-transfection社)を用いて腫瘍内投与を行った(3週間、計6回投与)。原発巣の腫瘍サイズは1週間に一度ずつノギスにより計測した(図6A)。移植44日後にマウスを解剖し、肺への転移の程度に関する評価を行った。肺組織の切片を作製し、抗ヒト・ビメンチン抗体による免疫組織染色を行った。各マウスにおいて同抗体で陽性となる微小転移数を計測し、1mm2あたりの微小転移数を計算した(図6B)。その結果、NAPGに対するsiRNAを投与したマウスでは陰性対照となるsiRNAを投与したマウスに比べて、原発巣の腫瘍サイズに差は見られなかったが、肺への微小転移数が有意に減少していた。
配列表の配列番号2は、ヒトNAPGのポリペプチドである。
配列表の配列番号3は、ヒトHINT3のmRNAの塩基配列である。
配列表の配列番号4は、ヒトHINT3のポリペプチドである。
配列表の配列番号5は、ヒトGXLT1のmRNAの塩基配列である。
配列表の配列番号6は、ヒトGXLT1のポリペプチドである。
Claims (11)
- NAPG、HINT3又はGXYLT1遺伝子の発現を抑制する物質を含有し、
該遺伝子の発現を抑制する物質が、該遺伝子のsiRNA、miRNA、アンチセンスオリゴヌクレオチド、リボザイム、及びこれらの発現ベクターからなる群より選ばれる1種以上である、実験試薬用のエクソソーム分泌阻害剤。 - HINT3又はGXYLT1遺伝子の発現を抑制する物質を含有し、
該遺伝子の発現を抑制する物質が、該遺伝子のsiRNA、miRNA(ただし、miR-194を除く)、アンチセンスオリゴヌクレオチド、リボザイム、及びこれらの発現ベクターからなる群より選ばれる1種以上である、エクソソーム分泌阻害剤。 - HINT3又はGXYLT1遺伝子の発現を抑制する物質を含有し、
該遺伝子の発現を抑制する物質が、該遺伝子のsiRNA、miRNA(ただし、miR-194を除く)、アンチセンスオリゴヌクレオチド、リボザイム、及びこれらの発現ベクターからなる群より選ばれる1種以上である、癌治療用又は癌転移抑制用の医薬組成物。 - 癌が前立腺癌又は乳癌である、請求項3に記載の医薬組成物。
- NAPG、HINT3又はGXYLT1遺伝子の発現を抑制する物質を含有し、
該遺伝子の発現を抑制する物質が、該遺伝子のsiRNA、miRNA、アンチセンスオリゴヌクレオチド、リボザイム、及びこれらの発現ベクターからなる群より選ばれる1種以上である、前立腺癌又は乳癌に対する癌治療用又は癌転移抑制用の医薬組成物。 - miR-194を含有してなる、実験試薬用のエクソソーム分泌阻害剤。
- NAPG、HINT3、若しくはGXYLT1遺伝子の発現又はNAPG、HINT3、若しくはGXYLT1タンパク質の活性を指標とし、これらの遺伝子の発現の抑制又はこれらのタンパク質の活性の抑制をする物質を候補化合物とする、エクソソーム分泌阻害用物質のスクリーニング方法。
- 下記の工程(a1)〜(c1)を含む、請求項7に記載のスクリーニング方法。
(a1)エクソソーム量の測定可能な細胞と被験物質とを接触させる工程
(b1)被験物質を接触させた細胞におけるエクソソーム量を測定し、該測定値を、被験物質を接触させない対照細胞におけるエクソソーム量と比較する工程
(c1)被験物質を接触させた細胞におけるエクソソーム量が、被験物質を接触させない対照細胞におけるエクソソーム量よりも低下している場合に、被験物質をエクソソーム分泌阻害用物質として選択する工程 - 下記の工程(a2)〜(c2)を含む、請求項7に記載のスクリーニング方法。
(a2)エクソソーム量の測定可能な細胞と被験物質とを接触させる工程
(b2)被験物質を接触させた細胞におけるエクソソーム量を測定し、該測定値を、予め測定しておいた被験物質を接触させる前の前記細胞におけるエクソソーム量と比較する工程
(c2)被験物質を接触させた細胞におけるエクソソーム量が、被験物質を接触させる前のエクソソーム量よりも低下している場合に、被験物質をエクソソーム分泌阻害用物質として選択する工程 - HINT3又はGXYLT1遺伝子の発現を抑制する物質を含有し、
該遺伝子の発現を抑制する物質が、該遺伝子のsiRNA、miRNA(ただし、miR-194を除く)、アンチセンスオリゴヌクレオチド、リボザイム、及びこれらの発現ベクターからなる群より選ばれる1種以上である、肺への癌転移抑制用の医薬組成物。 - 前立腺癌又は乳癌から肺への癌転移抑制用である、請求項10に記載の医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015177552 | 2015-09-09 | ||
JP2015177552 | 2015-09-09 | ||
PCT/JP2016/075324 WO2017043370A1 (ja) | 2015-09-09 | 2016-08-30 | エクソソーム分泌阻害剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2017043370A1 JPWO2017043370A1 (ja) | 2018-07-26 |
JP6895175B2 true JP6895175B2 (ja) | 2021-06-30 |
Family
ID=58239685
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017539125A Active JP6895175B2 (ja) | 2015-09-09 | 2016-08-30 | エクソソーム分泌阻害剤 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20190185851A1 (ja) |
EP (1) | EP3348278A4 (ja) |
JP (1) | JP6895175B2 (ja) |
CN (1) | CN108136019A (ja) |
CA (1) | CA2997674A1 (ja) |
WO (1) | WO2017043370A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020514325A (ja) | 2017-02-23 | 2020-05-21 | サンフォード ヘルス | 腫瘍治療のためのエフリンb1阻害剤 |
JP6899110B2 (ja) * | 2017-03-21 | 2021-07-07 | 国立大学法人東海国立大学機構 | 細胞増殖抑制剤およびがんの予防・治療剤 |
JP2021515570A (ja) * | 2018-03-14 | 2021-06-24 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアThe Regents Of The University Of California | 癌におけるおよび免疫抑制のための抑制性エキソソーム |
KR102268983B1 (ko) * | 2019-09-11 | 2021-06-24 | 경북대학교 산학협력단 | 엔도테린 수용체 억제제에 의한 엑소좀 분비 억제 또는 pd-l1 발현 억제 용도 |
EP4134097A1 (en) * | 2020-04-07 | 2023-02-15 | THEORIA Science Inc. | Extracellular vesicle secretion inhibitor for inhibiting extracellular vesicle secretion, and use of the same |
IT202100010001A1 (it) * | 2021-04-20 | 2022-10-20 | Univ Politecnica Delle Marche | Mirna per il trattamento terapeutico di tumori |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW200413725A (en) * | 2002-09-30 | 2004-08-01 | Oncotherapy Science Inc | Method for diagnosing non-small cell lung cancers |
EP2494360B1 (en) * | 2009-10-26 | 2017-08-16 | Abbott Molecular Inc. | Diagnostic methods for determining prognosis of non-small cell lung cancer |
HUE031912T2 (en) * | 2010-11-24 | 2017-08-28 | Hamlet Pharma Ab | Biologically active complex and production |
-
2016
- 2016-08-30 US US15/758,600 patent/US20190185851A1/en not_active Abandoned
- 2016-08-30 JP JP2017539125A patent/JP6895175B2/ja active Active
- 2016-08-30 EP EP16844231.7A patent/EP3348278A4/en not_active Withdrawn
- 2016-08-30 CN CN201680052563.2A patent/CN108136019A/zh active Pending
- 2016-08-30 WO PCT/JP2016/075324 patent/WO2017043370A1/ja active Application Filing
- 2016-08-30 CA CA2997674A patent/CA2997674A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
CA2997674A1 (en) | 2017-03-16 |
JPWO2017043370A1 (ja) | 2018-07-26 |
WO2017043370A1 (ja) | 2017-03-16 |
CN108136019A (zh) | 2018-06-08 |
EP3348278A1 (en) | 2018-07-18 |
US20190185851A1 (en) | 2019-06-20 |
EP3348278A4 (en) | 2019-04-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6895175B2 (ja) | エクソソーム分泌阻害剤 | |
CN109312341B (zh) | 微小rna及其使用方法 | |
JP6010458B2 (ja) | 非対称二本鎖rnaによる特異的阻害のための、方法および組成物 | |
JP4505749B2 (ja) | Bcl−2の発現抑制をするオリゴ二本鎖RNAとそれを含有する医薬組成物 | |
JP5976643B2 (ja) | 二本鎖rnaによるベータ−カテニンの特異的阻害に対する方法と組成物 | |
US20160024597A1 (en) | miRNAs AS THERAPEUTIC TARGETS IN CANCER | |
JP2020534354A (ja) | トリプルネガティブ乳癌の治療方法 | |
JP7376873B2 (ja) | がん促進因子発現抑制剤、その有効成分のスクリーニング方法、該方法に有用な発現カセット、診断薬、及び診断方法 | |
AU2015229033A1 (en) | Asymmetric interfering RNA compositions that silence K-Ras and methods of uses thereof | |
CN114025798B (zh) | 癌干细胞标记物以及癌干细胞靶向药物 | |
TW201119681A (en) | Compositions and methods for inhibiting expression of KIF10 genes | |
US8921333B2 (en) | Therapeutic agent for tumor | |
JP6436477B2 (ja) | 癌治療用医薬組成物 | |
US11319541B2 (en) | Anticancer therapeutic intervention | |
WO2015156237A1 (ja) | 慢性腎臓病治療用医薬組成物 | |
EP3994145A1 (en) | Inhibitors of rna editing and uses thereof | |
EP4019634A2 (en) | Compounds and methods for treating cancer | |
WO2012020839A1 (ja) | 癌治療用医薬組成物 | |
KR101445921B1 (ko) | miR-185의 항암적 용도 | |
US20230374508A1 (en) | Compositions and Methods Targeting circ2082 for the Treatment of Cancer | |
CN115212308B (zh) | Gasdermin e通路的靶向剂在治疗胰腺癌中的应用 | |
JP2010529852A (ja) | 癌治療のためのNuMAのRNAi媒介ノックダウン | |
JP7226763B2 (ja) | 癌幹細胞における薬物耐性の低減剤、癌幹細胞における転移能の抑制剤及び癌の転移性再発リスクを予測する方法 | |
KR100992239B1 (ko) | Mig12 유전자의 신규한 용도 | |
TW202400193A (zh) | 抑制跨膜絲胺酸蛋白酶6(tmprss6)表現的組成物及方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180301 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190515 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200427 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200625 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200826 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210120 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210317 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210407 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20210408 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20210412 |
|
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: 20210510 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210531 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6895175 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |