JP6757935B2 - 分子マンモグラフィ - Google Patents
分子マンモグラフィ Download PDFInfo
- Publication number
- JP6757935B2 JP6757935B2 JP2016570087A JP2016570087A JP6757935B2 JP 6757935 B2 JP6757935 B2 JP 6757935B2 JP 2016570087 A JP2016570087 A JP 2016570087A JP 2016570087 A JP2016570087 A JP 2016570087A JP 6757935 B2 JP6757935 B2 JP 6757935B2
- Authority
- JP
- Japan
- Prior art keywords
- mir
- breast
- individual
- use according
- cells
- 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.)
- Expired - Fee Related
Links
- 238000009607 mammography Methods 0.000 title claims description 100
- 239000012530 fluid Substances 0.000 claims description 157
- 210000000481 breast Anatomy 0.000 claims description 123
- 238000000034 method Methods 0.000 claims description 97
- 108091070501 miRNA Proteins 0.000 claims description 88
- 239000002679 microRNA Substances 0.000 claims description 88
- 230000005856 abnormality Effects 0.000 claims description 40
- -1 elibrin Chemical compound 0.000 claims description 40
- 239000003814 drug Substances 0.000 claims description 38
- 229940124597 therapeutic agent Drugs 0.000 claims description 36
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 32
- 230000003902 lesion Effects 0.000 claims description 32
- 210000002445 nipple Anatomy 0.000 claims description 29
- 230000007067 DNA methylation Effects 0.000 claims description 28
- 208000037396 Intraductal Noninfiltrating Carcinoma Diseases 0.000 claims description 28
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 26
- 239000000090 biomarker Substances 0.000 claims description 21
- 229960004679 doxorubicin Drugs 0.000 claims description 16
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 claims description 16
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 claims description 15
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 15
- 101800000989 Oxytocin Proteins 0.000 claims description 13
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 claims description 13
- 229930012538 Paclitaxel Natural products 0.000 claims description 13
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 claims description 13
- 229960001723 oxytocin Drugs 0.000 claims description 13
- 229960001592 paclitaxel Drugs 0.000 claims description 13
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 13
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 12
- 229960004397 cyclophosphamide Drugs 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 229960001603 tamoxifen Drugs 0.000 claims description 10
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 9
- 229960001904 epirubicin Drugs 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 8
- 108091029500 miR-183 stem-loop Proteins 0.000 claims description 8
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 7
- 108010066816 Polypeptide N-acetylgalactosaminyltransferase Proteins 0.000 claims description 7
- 229960002949 fluorouracil Drugs 0.000 claims description 7
- 108091049679 miR-20a stem-loop Proteins 0.000 claims description 7
- 229960000575 trastuzumab Drugs 0.000 claims description 7
- NYDCDZSEEAUOHN-IZHYLOQSSA-N N-Desmethyltamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCNC)=CC=1)/C1=CC=CC=C1 NYDCDZSEEAUOHN-IZHYLOQSSA-N 0.000 claims description 6
- 239000000427 antigen Substances 0.000 claims description 6
- 108091007433 antigens Proteins 0.000 claims description 6
- 102000036639 antigens Human genes 0.000 claims description 6
- 108091091751 miR-17 stem-loop Proteins 0.000 claims description 6
- 108091031103 miR-181a stem-loop Proteins 0.000 claims description 6
- 108091046591 miR-181a-4 stem-loop Proteins 0.000 claims description 6
- 108091049627 miR-181a-5 stem-loop Proteins 0.000 claims description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 6
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 claims description 5
- 229960002932 anastrozole Drugs 0.000 claims description 5
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 claims description 5
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 5
- 229960004562 carboplatin Drugs 0.000 claims description 5
- 229960000255 exemestane Drugs 0.000 claims description 5
- 239000012022 methylating agents Substances 0.000 claims description 5
- 108091058688 miR-141 stem-loop Proteins 0.000 claims description 5
- 108091063348 miR-193 stem-loop Proteins 0.000 claims description 5
- 108091036762 miR-193a stem-loop Proteins 0.000 claims description 5
- 108091039097 miR-193b stem-loop Proteins 0.000 claims description 5
- 108091063344 miR-30b stem-loop Proteins 0.000 claims description 5
- 108091057431 miR-30d stem-loop Proteins 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 229940125944 selective estrogen receptor degrader Drugs 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- MHJBZVSGOZTKRH-IZHYLOQSSA-N 4-Hydroxy-N-desmethyltamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCNC)=CC=1)/C1=CC=C(O)C=C1 MHJBZVSGOZTKRH-IZHYLOQSSA-N 0.000 claims description 4
- 108010088751 Albumins Proteins 0.000 claims description 4
- 102000009027 Albumins Human genes 0.000 claims description 4
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 4
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 4
- 108091007774 MIR107 Proteins 0.000 claims description 4
- 108091007772 MIRLET7C Proteins 0.000 claims description 4
- 108091027766 Mir-143 Proteins 0.000 claims description 4
- 108091028684 Mir-145 Proteins 0.000 claims description 4
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 4
- 239000012190 activator Substances 0.000 claims description 4
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 4
- 229960004316 cisplatin Drugs 0.000 claims description 4
- 229960003668 docetaxel Drugs 0.000 claims description 4
- 229960005167 everolimus Drugs 0.000 claims description 4
- 238000001125 extrusion Methods 0.000 claims description 4
- 229960005277 gemcitabine Drugs 0.000 claims description 4
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 229960001320 lapatinib ditosylate Drugs 0.000 claims description 4
- 108091044046 miR-17-1 stem-loop Proteins 0.000 claims description 4
- 108091065423 miR-17-3 stem-loop Proteins 0.000 claims description 4
- 108091089775 miR-200b stem-loop Proteins 0.000 claims description 4
- 108091092722 miR-23b stem-loop Proteins 0.000 claims description 4
- 108091031298 miR-23b-1 stem-loop Proteins 0.000 claims description 4
- 108091082339 miR-23b-2 stem-loop Proteins 0.000 claims description 4
- 108091061970 miR-26a stem-loop Proteins 0.000 claims description 4
- 108091071822 miR-572 stem-loop Proteins 0.000 claims description 4
- 229960001156 mitoxantrone Drugs 0.000 claims description 4
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 4
- AZBFJBJXUQUQLF-UHFFFAOYSA-N n-(1,5-dimethylpyrrolidin-3-yl)pyrrolidine-1-carboxamide Chemical compound C1N(C)C(C)CC1NC(=O)N1CCCC1 AZBFJBJXUQUQLF-UHFFFAOYSA-N 0.000 claims description 4
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims description 4
- 229930003347 Atropine Natural products 0.000 claims description 3
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 claims description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 3
- 108091028080 MiR-132 Proteins 0.000 claims description 3
- 108091028049 Mir-221 microRNA Proteins 0.000 claims description 3
- 108700025695 Suppressor Genes Proteins 0.000 claims description 3
- 229940123237 Taxane Drugs 0.000 claims description 3
- 229930003316 Vitamin D Natural products 0.000 claims description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 3
- 229940022663 acetate Drugs 0.000 claims description 3
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 3
- 230000000259 anti-tumor effect Effects 0.000 claims description 3
- 229960000396 atropine Drugs 0.000 claims description 3
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 claims description 3
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 claims description 3
- 238000003384 imaging method Methods 0.000 claims description 3
- 229960000485 methotrexate Drugs 0.000 claims description 3
- 108091074450 miR-200c stem-loop Proteins 0.000 claims description 3
- 108091045665 miR-202 stem-loop Proteins 0.000 claims description 3
- 108091031479 miR-204 stem-loop Proteins 0.000 claims description 3
- 108091032382 miR-204-1 stem-loop Proteins 0.000 claims description 3
- 108091085803 miR-204-2 stem-loop Proteins 0.000 claims description 3
- 108091089766 miR-204-3 stem-loop Proteins 0.000 claims description 3
- 108091073500 miR-204-4 stem-loop Proteins 0.000 claims description 3
- 108091053626 miR-204-5 stem-loop Proteins 0.000 claims description 3
- 108091062762 miR-21 stem-loop Proteins 0.000 claims description 3
- 108091041631 miR-21-1 stem-loop Proteins 0.000 claims description 3
- 108091044442 miR-21-2 stem-loop Proteins 0.000 claims description 3
- 108091061917 miR-221 stem-loop Proteins 0.000 claims description 3
- 108091063489 miR-221-1 stem-loop Proteins 0.000 claims description 3
- 108091055391 miR-221-2 stem-loop Proteins 0.000 claims description 3
- 108091031076 miR-221-3 stem-loop Proteins 0.000 claims description 3
- 108091088477 miR-29a stem-loop Proteins 0.000 claims description 3
- 108091029716 miR-29a-1 stem-loop Proteins 0.000 claims description 3
- 108091092089 miR-29a-2 stem-loop Proteins 0.000 claims description 3
- 108091066559 miR-29a-3 stem-loop Proteins 0.000 claims description 3
- 108091031484 miR-335 stem-loop Proteins 0.000 claims description 3
- 108091048468 miR-383 stem-loop Proteins 0.000 claims description 3
- 108091044133 miR-454 stem-loop Proteins 0.000 claims description 3
- 108091063340 miR-497 stem-loop Proteins 0.000 claims description 3
- 108091031110 miR-539 stem-loop Proteins 0.000 claims description 3
- 108091063333 miR-556 stem-loop Proteins 0.000 claims description 3
- 108091038240 miR-638 stem-loop Proteins 0.000 claims description 3
- 108091063911 miR-650 stem-loop Proteins 0.000 claims description 3
- 108091092761 miR-671 stem-loop Proteins 0.000 claims description 3
- 108091034121 miR-92a stem-loop Proteins 0.000 claims description 3
- 108091041519 miR-92a-3 stem-loop Proteins 0.000 claims description 3
- 235000020660 omega-3 fatty acid Nutrition 0.000 claims description 3
- 229940012843 omega-3 fatty acid Drugs 0.000 claims description 3
- 229960002087 pertuzumab Drugs 0.000 claims description 3
- 229910052697 platinum Inorganic materials 0.000 claims description 3
- 239000000333 selective estrogen receptor modulator Substances 0.000 claims description 3
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 3
- 235000019166 vitamin D Nutrition 0.000 claims description 3
- 239000011710 vitamin D Substances 0.000 claims description 3
- 229940046008 vitamin d Drugs 0.000 claims description 3
- FVVPWVFWOOMXEZ-ZIADKAODSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-(4-propan-2-ylphenyl)but-1-enyl]phenol Chemical compound C=1C=C(C(C)C)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=C(O)C=C1 FVVPWVFWOOMXEZ-ZIADKAODSA-N 0.000 claims description 2
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 2
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 claims description 2
- 108091027559 Mir-96 microRNA Proteins 0.000 claims description 2
- 108091033760 Oncomir Proteins 0.000 claims description 2
- 229960004117 capecitabine Drugs 0.000 claims description 2
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 claims description 2
- 229960002258 fulvestrant Drugs 0.000 claims description 2
- 108091063986 let-7f stem-loop Proteins 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 108091045790 miR-106b stem-loop Proteins 0.000 claims description 2
- 108091023403 miR-1202 stem-loop Proteins 0.000 claims description 2
- 108091054042 miR-1207 stem-loop Proteins 0.000 claims description 2
- 108091056924 miR-124 stem-loop Proteins 0.000 claims description 2
- 108091074816 miR-1268 stem-loop Proteins 0.000 claims description 2
- 108091046573 miR-1275 stem-loop Proteins 0.000 claims description 2
- 108091040501 miR-129 stem-loop Proteins 0.000 claims description 2
- 108091045757 miR-129-3 stem-loop Proteins 0.000 claims description 2
- 108091090758 miR-129-4 stem-loop Proteins 0.000 claims description 2
- 108091065139 miR-129-5 stem-loop Proteins 0.000 claims description 2
- 108091045872 miR-135 stem-loop Proteins 0.000 claims description 2
- 108091026523 miR-135a stem-loop Proteins 0.000 claims description 2
- 108091026375 miR-135b stem-loop Proteins 0.000 claims description 2
- 108091086065 miR-135b-2 stem-loop Proteins 0.000 claims description 2
- 108091031326 miR-15b stem-loop Proteins 0.000 claims description 2
- 108091069239 miR-17-2 stem-loop Proteins 0.000 claims description 2
- 108091023567 miR-1915 stem-loop Proteins 0.000 claims description 2
- 108091037787 miR-19b stem-loop Proteins 0.000 claims description 2
- 108091035428 miR-3143 stem-loop Proteins 0.000 claims description 2
- 108091036962 miR-3672 stem-loop Proteins 0.000 claims description 2
- 108091027983 miR-378-1 stem-loop Proteins 0.000 claims description 2
- 108091089716 miR-378-2 stem-loop Proteins 0.000 claims description 2
- 108091090987 miR-425 stem-loop Proteins 0.000 claims description 2
- 108091086430 miR-4324 stem-loop Proteins 0.000 claims description 2
- 108091069917 miR-491 stem-loop Proteins 0.000 claims description 2
- 108091090896 miR-506 stem-loop Proteins 0.000 claims description 2
- 108091045812 miR-544b stem-loop Proteins 0.000 claims description 2
- 108091076617 miR-544b-1 stem-loop Proteins 0.000 claims description 2
- 108091050743 miR-544b-2 stem-loop Proteins 0.000 claims description 2
- 108091069948 miR-548a-1 stem-loop Proteins 0.000 claims description 2
- 108091073707 miR-548a-2 stem-loop Proteins 0.000 claims description 2
- 108091034066 miR-548a-3 stem-loop Proteins 0.000 claims description 2
- 108091068733 miR-548e stem-loop Proteins 0.000 claims description 2
- 108091071062 miR-557 stem-loop Proteins 0.000 claims description 2
- 108091046865 miR-569 stem-loop Proteins 0.000 claims description 2
- 108091023843 miR-575 stem-loop Proteins 0.000 claims description 2
- 108091024411 miR-590 stem-loop Proteins 0.000 claims description 2
- 108091024127 miR-634 stem-loop Proteins 0.000 claims description 2
- 108091049434 miR-644 stem-loop Proteins 0.000 claims description 2
- 108091084058 miR-874 stem-loop Proteins 0.000 claims description 2
- 108091058491 miR-877 stem-loop Proteins 0.000 claims description 2
- 108091030513 miR-933 stem-loop Proteins 0.000 claims description 2
- 108091086713 miR-96 stem-loop Proteins 0.000 claims description 2
- 108091070961 miR-96-3 stem-loop Proteins 0.000 claims description 2
- 108091024443 miRa-135-1 stem-loop Proteins 0.000 claims description 2
- 229950008642 miproxifene Drugs 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 229960004622 raloxifene Drugs 0.000 claims description 2
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 2
- 229960005026 toremifene Drugs 0.000 claims description 2
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 claims description 2
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 claims 2
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 108091091360 miR-125b stem-loop Proteins 0.000 claims 1
- 108091070946 miR-128 stem-loop Proteins 0.000 claims 1
- 108091032320 miR-146 stem-loop Proteins 0.000 claims 1
- 108091024530 miR-146a stem-loop Proteins 0.000 claims 1
- 108091087148 miR-20 stem-loop Proteins 0.000 claims 1
- 108091066984 miR-20-1 stem-loop Proteins 0.000 claims 1
- 108091076199 miR-20-2 stem-loop Proteins 0.000 claims 1
- 108091087149 miR-2171 stem-loop Proteins 0.000 claims 1
- 108091007432 miR-29b Proteins 0.000 claims 1
- 108091059493 miR-322 stem-loop Proteins 0.000 claims 1
- 108091049667 miR-340 stem-loop Proteins 0.000 claims 1
- 108091057189 miR-340-2 stem-loop Proteins 0.000 claims 1
- 108091029119 miR-34a stem-loop Proteins 0.000 claims 1
- 108091091625 miR-519c stem-loop Proteins 0.000 claims 1
- 108091026826 miR-519c-2 stem-loop Proteins 0.000 claims 1
- 108091032902 miR-93 stem-loop Proteins 0.000 claims 1
- 229940095743 selective estrogen receptor modulator Drugs 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 115
- 239000000523 sample Substances 0.000 description 114
- 206010028980 Neoplasm Diseases 0.000 description 90
- 238000000338 in vitro Methods 0.000 description 82
- 206010006187 Breast cancer Diseases 0.000 description 79
- 208000026310 Breast neoplasm Diseases 0.000 description 79
- 201000011510 cancer Diseases 0.000 description 56
- 239000002250 absorbent Substances 0.000 description 40
- 230000002745 absorbent Effects 0.000 description 40
- 206010020718 hyperplasia Diseases 0.000 description 40
- 108090000623 proteins and genes Proteins 0.000 description 39
- 238000012216 screening Methods 0.000 description 39
- 102100027881 Tumor protein 63 Human genes 0.000 description 31
- 101710140697 Tumor protein 63 Proteins 0.000 description 30
- 101710087047 Cytoskeleton-associated protein 4 Proteins 0.000 description 29
- 108020004414 DNA Proteins 0.000 description 26
- 238000003745 diagnosis Methods 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 24
- 201000010099 disease Diseases 0.000 description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
- 238000004393 prognosis Methods 0.000 description 23
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 19
- 210000005075 mammary gland Anatomy 0.000 description 19
- 239000002609 medium Substances 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 230000011987 methylation Effects 0.000 description 17
- 238000007069 methylation reaction Methods 0.000 description 17
- 239000007790 solid phase Substances 0.000 description 17
- 206010006256 Breast hyperplasia Diseases 0.000 description 16
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 15
- 206010073094 Intraductal proliferative breast lesion Diseases 0.000 description 15
- 201000007273 ductal carcinoma in situ Diseases 0.000 description 15
- 238000012163 sequencing technique Methods 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 14
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 12
- 102400000050 Oxytocin Human genes 0.000 description 12
- 238000002648 combination therapy Methods 0.000 description 12
- 238000003752 polymerase chain reaction Methods 0.000 description 12
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 11
- 239000002773 nucleotide Substances 0.000 description 10
- 125000003729 nucleotide group Chemical group 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 101710120843 Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 9
- 239000000020 Nitrocellulose Substances 0.000 description 9
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 229920001220 nitrocellulos Polymers 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 102100040062 Indoleamine 2,3-dioxygenase 2 Human genes 0.000 description 8
- 101710120841 Indoleamine 2,3-dioxygenase 2 Proteins 0.000 description 8
- 239000011324 bead Substances 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 8
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 102000011782 Keratins Human genes 0.000 description 7
- 108010076876 Keratins Proteins 0.000 description 7
- 208000030270 breast disease Diseases 0.000 description 7
- 108700021293 carbetocin Proteins 0.000 description 7
- 229960001118 carbetocin Drugs 0.000 description 7
- NSTRIRCPWQHTIA-DTRKZRJBSA-N carbetocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSCCCC(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(OC)C=C1 NSTRIRCPWQHTIA-DTRKZRJBSA-N 0.000 description 7
- 238000003753 real-time PCR Methods 0.000 description 7
- 208000009458 Carcinoma in Situ Diseases 0.000 description 6
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- 210000004883 areola Anatomy 0.000 description 6
- 208000024119 breast tumor luminal A or B Diseases 0.000 description 6
- 239000007795 chemical reaction product Substances 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- QCQYVCMYGCHVMR-AAZUGDAUSA-N n-[(2r,3r,4s,5r)-4,5,6-trihydroxy-1-oxo-3-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexan-2-yl]acetamide Chemical compound CC(=O)N[C@@H](C=O)[C@H]([C@@H](O)[C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O QCQYVCMYGCHVMR-AAZUGDAUSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 5
- 108010033040 Histones Proteins 0.000 description 5
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 5
- 108700011259 MicroRNAs Proteins 0.000 description 5
- WLDHEUZGFKACJH-UHFFFAOYSA-K amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1N=NC1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-UHFFFAOYSA-K 0.000 description 5
- 208000010572 basal-like breast carcinoma Diseases 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 5
- 210000002777 columnar cell Anatomy 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 201000004933 in situ carcinoma Diseases 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- 238000002493 microarray Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 239000013615 primer Substances 0.000 description 5
- 238000011269 treatment regimen Methods 0.000 description 5
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108091029523 CpG island Proteins 0.000 description 4
- 230000026641 DNA hypermethylation Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229930186217 Glycolipid Natural products 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 4
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 102000015694 estrogen receptors Human genes 0.000 description 4
- 108010038795 estrogen receptors Proteins 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 239000011859 microparticle Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000013618 particulate matter Substances 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 206010064571 Gene mutation Diseases 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 3
- 108020005196 Mitochondrial DNA Proteins 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 208000028176 atypical lobular breast hyperplasia Diseases 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 210000005081 epithelial layer Anatomy 0.000 description 3
- 201000007281 estrogen-receptor positive breast cancer Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 238000001794 hormone therapy Methods 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 208000030776 invasive breast carcinoma Diseases 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 238000004223 overdiagnosis Methods 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 102000054765 polymorphisms of proteins Human genes 0.000 description 3
- 102000040430 polynucleotide Human genes 0.000 description 3
- 108091033319 polynucleotide Proteins 0.000 description 3
- 239000002157 polynucleotide Substances 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000003757 reverse transcription PCR Methods 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 241000321096 Adenoides Species 0.000 description 2
- 108700020463 BRCA1 Proteins 0.000 description 2
- 102000036365 BRCA1 Human genes 0.000 description 2
- 101150072950 BRCA1 gene Proteins 0.000 description 2
- 108700020462 BRCA2 Proteins 0.000 description 2
- 102000052609 BRCA2 Human genes 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 101150008921 Brca2 gene Proteins 0.000 description 2
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- 101000677545 Homo sapiens Long-chain specific acyl-CoA dehydrogenase, mitochondrial Proteins 0.000 description 2
- 101000710013 Homo sapiens Reversion-inducing cysteine-rich protein with Kazal motifs Proteins 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 102100021644 Long-chain specific acyl-CoA dehydrogenase, mitochondrial Human genes 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102000003729 Neprilysin Human genes 0.000 description 2
- 108090000028 Neprilysin Proteins 0.000 description 2
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 2
- 208000012868 Overgrowth Diseases 0.000 description 2
- 108010032788 PAX6 Transcription Factor Proteins 0.000 description 2
- 102000007354 PAX6 Transcription Factor Human genes 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 238000003559 RNA-seq method Methods 0.000 description 2
- 101150020421 SFR2 gene Proteins 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 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 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 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 210000002534 adenoid Anatomy 0.000 description 2
- 229940061720 alpha hydroxy acid Drugs 0.000 description 2
- 150000001280 alpha hydroxy acids Chemical class 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 150000001277 beta hydroxy acids Chemical class 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 238000001369 bisulfite sequencing Methods 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000006059 cover glass Substances 0.000 description 2
- 230000002380 cytological effect Effects 0.000 description 2
- 238000012350 deep sequencing Methods 0.000 description 2
- 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 2
- 229940079593 drug Drugs 0.000 description 2
- 238000009585 enzyme analysis Methods 0.000 description 2
- 210000001808 exosome Anatomy 0.000 description 2
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
- 210000001703 glandular epithelial cell Anatomy 0.000 description 2
- 102000051957 human ERBB2 Human genes 0.000 description 2
- 230000006607 hypermethylation Effects 0.000 description 2
- 238000012151 immunohistochemical method Methods 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 2
- 230000002262 irrigation Effects 0.000 description 2
- 238000003973 irrigation Methods 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 238000007834 ligase chain reaction Methods 0.000 description 2
- 208000026535 luminal A breast carcinoma Diseases 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 150000002736 metal compounds Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 108091064355 mitochondrial RNA Proteins 0.000 description 2
- 238000007481 next generation sequencing Methods 0.000 description 2
- 239000002751 oligonucleotide probe Substances 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 102000003998 progesterone receptors Human genes 0.000 description 2
- 108090000468 progesterone receptors Proteins 0.000 description 2
- 238000000275 quality assurance Methods 0.000 description 2
- 239000002096 quantum dot Substances 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000007841 sequencing by ligation Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- BURHGPHDEVGCEZ-KJGLQBJMSA-N (e)-3-[4-[(e)-2-(2-chloro-4-fluorophenyl)-1-(1h-indazol-5-yl)but-1-enyl]phenyl]prop-2-enoic acid Chemical compound C=1C=C(F)C=C(Cl)C=1C(/CC)=C(C=1C=C2C=NNC2=CC=1)\C1=CC=C(\C=C\C(O)=O)C=C1 BURHGPHDEVGCEZ-KJGLQBJMSA-N 0.000 description 1
- HYOAGWAIGJXNQH-UHFFFAOYSA-N 1-bromo-1-chloropropane Chemical compound CCC(Cl)Br HYOAGWAIGJXNQH-UHFFFAOYSA-N 0.000 description 1
- 108020004465 16S ribosomal RNA Proteins 0.000 description 1
- HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 description 1
- 210000002925 A-like Anatomy 0.000 description 1
- 208000019738 Abnormality of the breast Diseases 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 102100032438 Beta-1,3-galactosyltransferase 1 Human genes 0.000 description 1
- 102100023993 Beta-1,3-galactosyltransferase 5 Human genes 0.000 description 1
- 102100026008 Breakpoint cluster region protein Human genes 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 102100024152 Cadherin-17 Human genes 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- 208000004434 Calcinosis Diseases 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- CXRFDZFCGOPDTD-UHFFFAOYSA-M Cetrimide Chemical compound [Br-].CCCCCCCCCCCCCC[N+](C)(C)C CXRFDZFCGOPDTD-UHFFFAOYSA-M 0.000 description 1
- 241000251556 Chordata Species 0.000 description 1
- 206010008805 Chromosomal abnormalities Diseases 0.000 description 1
- 208000031404 Chromosome Aberrations Diseases 0.000 description 1
- 102100033772 Complement C4-A Human genes 0.000 description 1
- 108091029430 CpG site Proteins 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- 230000009946 DNA mutation Effects 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 102000016680 Dioxygenases Human genes 0.000 description 1
- 108010028143 Dioxygenases Proteins 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000006402 Ductal Carcinoma Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 102100037738 Fatty acid-binding protein, heart Human genes 0.000 description 1
- 102100028461 Frizzled-9 Human genes 0.000 description 1
- 108060003306 Galactosyltransferase Proteins 0.000 description 1
- 102000030902 Galactosyltransferase Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 102100031493 Growth arrest-specific protein 7 Human genes 0.000 description 1
- 108010006464 Hemolysin Proteins Proteins 0.000 description 1
- 102100038720 Histone deacetylase 9 Human genes 0.000 description 1
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 description 1
- 102100030308 Homeobox protein Hox-A11 Human genes 0.000 description 1
- 102100021090 Homeobox protein Hox-A9 Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000792933 Homo sapiens AT-rich interactive domain-containing protein 4A Proteins 0.000 description 1
- 101000798380 Homo sapiens Beta-1,3-galactosyltransferase 1 Proteins 0.000 description 1
- 101000904597 Homo sapiens Beta-1,3-galactosyltransferase 5 Proteins 0.000 description 1
- 101000933320 Homo sapiens Breakpoint cluster region protein Proteins 0.000 description 1
- 101000762247 Homo sapiens Cadherin-17 Proteins 0.000 description 1
- 101000710884 Homo sapiens Complement C4-A Proteins 0.000 description 1
- 101000710883 Homo sapiens Complement C4-B Proteins 0.000 description 1
- 101001027663 Homo sapiens Fatty acid-binding protein, heart Proteins 0.000 description 1
- 101001061405 Homo sapiens Frizzled-9 Proteins 0.000 description 1
- 101000923044 Homo sapiens Growth arrest-specific protein 7 Proteins 0.000 description 1
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 description 1
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 description 1
- 101001083158 Homo sapiens Homeobox protein Hox-A11 Proteins 0.000 description 1
- 101000614439 Homo sapiens Keratin, type I cytoskeletal 15 Proteins 0.000 description 1
- 101001034314 Homo sapiens Lactadherin Proteins 0.000 description 1
- 101000991061 Homo sapiens MHC class I polypeptide-related sequence B Proteins 0.000 description 1
- 101000629400 Homo sapiens Mesoderm-specific transcript homolog protein Proteins 0.000 description 1
- 101001053641 Homo sapiens Plasma serine protease inhibitor Proteins 0.000 description 1
- 101000712958 Homo sapiens Ras association domain-containing protein 1 Proteins 0.000 description 1
- 101001112293 Homo sapiens Retinoic acid receptor alpha Proteins 0.000 description 1
- 101000756373 Homo sapiens Retinol-binding protein 1 Proteins 0.000 description 1
- 101000739160 Homo sapiens Secretoglobin family 3A member 1 Proteins 0.000 description 1
- 101000654740 Homo sapiens Septin-5 Proteins 0.000 description 1
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 1
- 101000987003 Homo sapiens Tumor protein 63 Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 description 1
- 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 description 1
- 102100040443 Keratin, type I cytoskeletal 15 Human genes 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102100039648 Lactadherin Human genes 0.000 description 1
- 244000178870 Lavandula angustifolia Species 0.000 description 1
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 1
- VAYOSLLFUXYJDT-RDTXWAMCSA-N Lysergic acid diethylamide Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N(CC)CC)C2)=C3C2=CNC3=C1 VAYOSLLFUXYJDT-RDTXWAMCSA-N 0.000 description 1
- 102100030300 MHC class I polypeptide-related sequence B Human genes 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 102100026821 Mesoderm-specific transcript homolog protein Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 108091027977 Mir-200 Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 241001440127 Phyllodes Species 0.000 description 1
- 102100024078 Plasma serine protease inhibitor Human genes 0.000 description 1
- 229920012196 Polyoxymethylene Copolymer Polymers 0.000 description 1
- 108010069820 Pro-Opiomelanocortin Proteins 0.000 description 1
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 244000018633 Prunus armeniaca Species 0.000 description 1
- 235000009827 Prunus armeniaca Nutrition 0.000 description 1
- 102100033243 Ras association domain-containing protein 1 Human genes 0.000 description 1
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 description 1
- 102100022941 Retinol-binding protein 1 Human genes 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 102100037268 Secretoglobin family 3A member 1 Human genes 0.000 description 1
- 102100032744 Septin-5 Human genes 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 108010088412 Trefoil Factor-1 Proteins 0.000 description 1
- 102000008817 Trefoil Factor-1 Human genes 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 239000003082 abrasive agent Substances 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- TXUZVZSFRXZGTL-QPLCGJKRSA-N afimoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=C(O)C=C1 TXUZVZSFRXZGTL-QPLCGJKRSA-N 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000000035 biogenic effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000069 breast epithelial cell Anatomy 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 108091092259 cell-free RNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000002247 constant time method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000009274 differential gene expression Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 229960003649 eribulin Drugs 0.000 description 1
- UFNVPOGXISZXJD-XJPMSQCNSA-N eribulin Chemical compound C([C@H]1CC[C@@H]2O[C@@H]3[C@H]4O[C@H]5C[C@](O[C@H]4[C@H]2O1)(O[C@@H]53)CC[C@@H]1O[C@H](C(C1)=C)CC1)C(=O)C[C@@H]2[C@@H](OC)[C@@H](C[C@H](O)CN)O[C@H]2C[C@@H]2C(=C)[C@H](C)C[C@H]1O2 UFNVPOGXISZXJD-XJPMSQCNSA-N 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000002509 fluorescent in situ hybridization Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- CNKHSLKYRMDDNQ-UHFFFAOYSA-N halofenozide Chemical compound C=1C=CC=CC=1C(=O)N(C(C)(C)C)NC(=O)C1=CC=C(Cl)C=C1 CNKHSLKYRMDDNQ-UHFFFAOYSA-N 0.000 description 1
- 239000003228 hemolysin Substances 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 108010027263 homeobox protein HOXA9 Proteins 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 201000004653 inflammatory breast carcinoma Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000001102 lavandula vera Substances 0.000 description 1
- 235000018219 lavender Nutrition 0.000 description 1
- 108091091807 let-7a stem-loop Proteins 0.000 description 1
- 108091057746 let-7a-4 stem-loop Proteins 0.000 description 1
- 108091028376 let-7a-5 stem-loop Proteins 0.000 description 1
- 108091024393 let-7a-6 stem-loop Proteins 0.000 description 1
- 108091091174 let-7a-7 stem-loop Proteins 0.000 description 1
- 108091007423 let-7b Proteins 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- 208000026534 luminal B breast carcinoma Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000007403 mPCR Methods 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- MCPLVIGCWWTHFH-UHFFFAOYSA-L methyl blue Chemical compound [Na+].[Na+].C1=CC(S(=O)(=O)[O-])=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[NH+]C=2C=CC(=CC=2)S([O-])(=O)=O)C=2C=CC(NC=3C=CC(=CC=3)S([O-])(=O)=O)=CC=2)C=C1 MCPLVIGCWWTHFH-UHFFFAOYSA-L 0.000 description 1
- DWCZIOOZPIDHAB-UHFFFAOYSA-L methyl green Chemical compound [Cl-].[Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC(=CC=1)[N+](C)(C)C)=C1C=CC(=[N+](C)C)C=C1 DWCZIOOZPIDHAB-UHFFFAOYSA-L 0.000 description 1
- 108091027943 miR-16 stem-loop Proteins 0.000 description 1
- 108091035328 miR-217 stem-loop Proteins 0.000 description 1
- 108091039135 miR-217-1 stem-loop Proteins 0.000 description 1
- 108091029206 miR-217-2 stem-loop Proteins 0.000 description 1
- 108091048549 miR-29b stem-loop Proteins 0.000 description 1
- 108091092564 miR-494 stem-loop Proteins 0.000 description 1
- 108091030941 miR-554 stem-loop Proteins 0.000 description 1
- 108091050734 miR-652 stem-loop Proteins 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 201000010225 mixed cell type cancer Diseases 0.000 description 1
- 208000029638 mixed neoplasm Diseases 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- UYDLBVPAAFVANX-UHFFFAOYSA-N octylphenoxy polyethoxyethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCO)C=C1 UYDLBVPAAFVANX-UHFFFAOYSA-N 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 102000041788 p53 family Human genes 0.000 description 1
- 108091075611 p53 family Proteins 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- NTGBUUXKGAZMSE-UHFFFAOYSA-N phenyl n-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]carbamate Chemical compound C1=CC(OC)=CC=C1N1CCN(C=2C=CC(NC(=O)OC=3C=CC=CC=3)=CC=2)CC1 NTGBUUXKGAZMSE-UHFFFAOYSA-N 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 108091007428 primary miRNA Proteins 0.000 description 1
- 239000002987 primer (paints) Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000035803 proliferative type breast fibrocystic change Diseases 0.000 description 1
- 230000019639 protein methylation Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000005201 scrubbing Methods 0.000 description 1
- 210000002955 secretory cell Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000002978 thoracic duct Anatomy 0.000 description 1
- 229960001612 trastuzumab emtansine Drugs 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000007482 whole exome sequencing Methods 0.000 description 1
- 238000012070 whole genome sequencing analysis Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/112—Disease subtyping, staging or classification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/118—Prognosis of disease development
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/154—Methylation markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- General Engineering & Computer Science (AREA)
- Hospice & Palliative Care (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Reproductive Health (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Apparatus For Radiation Diagnosis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462007830P | 2014-06-04 | 2014-06-04 | |
| US62/007,830 | 2014-06-04 | ||
| PCT/US2015/033827 WO2015187727A2 (en) | 2014-06-04 | 2015-06-02 | Molecular mammography |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017527775A JP2017527775A (ja) | 2017-09-21 |
| JP2017527775A5 JP2017527775A5 (https=) | 2018-07-12 |
| JP6757935B2 true JP6757935B2 (ja) | 2020-09-23 |
Family
ID=54767566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016570087A Expired - Fee Related JP6757935B2 (ja) | 2014-06-04 | 2015-06-02 | 分子マンモグラフィ |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20170145515A1 (https=) |
| EP (1) | EP3152579A4 (https=) |
| JP (1) | JP6757935B2 (https=) |
| CN (1) | CN107076747B (https=) |
| WO (1) | WO2015187727A2 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107012199A (zh) * | 2016-01-28 | 2017-08-04 | 上海市东方医院 | 一种在血浆和血清中检测miRNA的方法 |
| JP6980219B2 (ja) * | 2016-08-22 | 2021-12-15 | いであ株式会社 | がんを検出、又はがんの進行期を判定する方法 |
| WO2018098379A1 (en) * | 2016-11-22 | 2018-05-31 | Prime Genomics, Inc. | Methods for cancer detection |
| TWI793165B (zh) | 2017-09-11 | 2023-02-21 | 美商阿托薩醫療公司 | 製造及使用因多昔芬(endoxifen)之方法 |
| JP7108715B2 (ja) * | 2018-01-25 | 2022-07-28 | パー ホール | 乳房障害の治療をモニターするための組成物および方法 |
| GB201907999D0 (en) * | 2019-06-05 | 2019-07-17 | Cambridge Entpr | Breast cancer detection methods |
| MX2022000203A (es) | 2019-07-03 | 2022-03-22 | Atossa Therapeutics Inc | Composiciones de liberacion sostenida de endoxifeno. |
| CN110760513A (zh) * | 2019-08-23 | 2020-02-07 | 西北工业大学 | 靶向三阴性乳腺癌细胞PENK基因的miR-506及其应用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5798266A (en) * | 1996-08-27 | 1998-08-25 | K-Quay Enterprises, Llc | Methods and kits for obtaining and assaying mammary fluid samples for breast diseases, including cancer |
| WO2003042660A2 (en) * | 2001-11-14 | 2003-05-22 | Sirbasku David A | Screening method for predicting susceptibility to breast cancer |
| CA2477828A1 (en) * | 2002-03-15 | 2003-09-25 | Cytyc Health Corporation | Method of diagnosis and treatment of breast lesions |
| WO2007140352A2 (en) * | 2006-05-26 | 2007-12-06 | Invitrogen Corporation | Plasma membrane and secreted cancer biomarkers |
| US8738124B2 (en) * | 2007-12-11 | 2014-05-27 | Epi-Sci, Llc | Electrical bioimpedance analysis as a biomarker of breast density and/or breast cancer risk |
| EP2358912B1 (en) * | 2008-10-30 | 2016-10-12 | Caris Life Sciences Switzerland Holdings GmbH | Methods for assessing rna patterns |
| GB2463401B (en) * | 2008-11-12 | 2014-01-29 | Caris Life Sciences Luxembourg Holdings S A R L | Characterizing prostate disorders by analysis of microvesicles |
| WO2011137288A2 (en) * | 2010-04-30 | 2011-11-03 | The Ohio State University | Mirna networks in cancers and leukemias and uses thereof |
| WO2013063147A1 (en) * | 2011-10-24 | 2013-05-02 | Atossa Genetics, Inc. | Absorbent paper and use thereof for breast cancer detection |
| US20130115629A1 (en) * | 2011-10-24 | 2013-05-09 | Atossa Genetics, Inc. | Methods of breast cancer detection |
-
2015
- 2015-06-02 CN CN201580039837.XA patent/CN107076747B/zh not_active Expired - Fee Related
- 2015-06-02 EP EP15803028.8A patent/EP3152579A4/en not_active Withdrawn
- 2015-06-02 US US15/316,136 patent/US20170145515A1/en not_active Abandoned
- 2015-06-02 WO PCT/US2015/033827 patent/WO2015187727A2/en not_active Ceased
- 2015-06-02 JP JP2016570087A patent/JP6757935B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP3152579A4 (en) | 2018-01-17 |
| CN107076747A (zh) | 2017-08-18 |
| WO2015187727A3 (en) | 2016-01-21 |
| CN107076747B (zh) | 2021-02-02 |
| JP2017527775A (ja) | 2017-09-21 |
| US20170145515A1 (en) | 2017-05-25 |
| WO2015187727A2 (en) | 2015-12-10 |
| EP3152579A2 (en) | 2017-04-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6757935B2 (ja) | 分子マンモグラフィ | |
| Ou et al. | Single‐nucleus RNA sequencing and spatial transcriptomics reveal the immunological microenvironment of cervical squamous cell carcinoma | |
| Ning et al. | Early diagnosis of lung cancer: which is the optimal choice? | |
| Zhang et al. | Liquid biopsy for cancer: circulating tumor cells, circulating free DNA or exosomes? | |
| EP2809801B1 (en) | Non-invasive cancer diagnosis | |
| Takeshita et al. | Serum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma | |
| US7888035B2 (en) | Methods for assessing RNA patterns | |
| Jovčevska | Sequencing the next generation of glioblastomas | |
| JP2019528081A (ja) | 子宮内膜症についてのバイオマーカーとしてのマイクロｒｎａ | |
| WO2013057567A1 (en) | Biomarkers useful for detection of types, grades and stages of human breast cancer | |
| WO2016109939A1 (zh) | 一种富集循环肿瘤dna的方法和试剂 | |
| Andreasen | Molecular features of adenoid cystic carcinoma with an emphasis on microRNA expression. | |
| Senaratne et al. | Clinical value of circulating microRNAs in diagnosis and prognosis of pancreatic cancer: A systematic review | |
| Delmonico et al. | Mutation profiling in the PIK3CA, TP53, and CDKN2A genes in circulating free DNA and impalpable breast lesions | |
| Nafar et al. | An investigation into cell-free DNA in different common cancers | |
| JP2011511635A (ja) | 癌標識としての結腸癌関連転写因子１（ｃｃａｔ−１） | |
| CN103773761B (zh) | 检测胃癌的血清/血浆微小rna标志物及其应用 | |
| Attia et al. | Altered expression of microRNAs in the bone marrow of multiple myeloma patients and their relationship to cytogenetic aberrations | |
| Gordon et al. | Genomic medicine for cancer diagnosis | |
| Pal et al. | Biomarkers as putative therapeutic targets in colorectal cancer | |
| González Martínez | El papel de los microARNs en el diagnóstico y pronóstico del cáncer de mama | |
| Morini | Bone Marrow-Derived Extracellular Vesicles Carry RNAs Shaping The Tumor Microenvironment in High-Risk Neuroblastoma Patients | |
| Bajpai et al. | Biomarkers of Esophageal Cancers and Precancerous Lesions | |
| Duréndez Sáez | Liquid Biopsy in non-small cell lung cancer: exosomes as a tool for the study of biomarkers. | |
| Zambelli | Analisi molecolare di forme aggressive di neoplasia endocrina per la identificazione di meccanismi di progressione e di potenziali nuovi bersagli terapeutici |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180125 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180530 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180531 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190509 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190806 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200120 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200417 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200612 |
|
| 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: 20200727 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200821 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6757935 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| LAPS | Cancellation because of no payment of annual fees |