JP7637509B2 - 大腸がんおよび進行腺腫をスクリーニングするためのキットおよびその応用 - Google Patents
大腸がんおよび進行腺腫をスクリーニングするためのキットおよびその応用 Download PDFInfo
- Publication number
- JP7637509B2 JP7637509B2 JP2020564893A JP2020564893A JP7637509B2 JP 7637509 B2 JP7637509 B2 JP 7637509B2 JP 2020564893 A JP2020564893 A JP 2020564893A JP 2020564893 A JP2020564893 A JP 2020564893A JP 7637509 B2 JP7637509 B2 JP 7637509B2
- Authority
- JP
- Japan
- Prior art keywords
- seq
- probe
- primer
- gene
- patient
- 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
- 206010009944 Colon cancer Diseases 0.000 title claims description 146
- 208000003200 Adenoma Diseases 0.000 title claims description 129
- 238000012216 screening Methods 0.000 title description 14
- 208000029742 colonic neoplasm Diseases 0.000 title description 3
- 239000000523 sample Substances 0.000 claims description 327
- 101000995332 Homo sapiens Protein NDRG4 Proteins 0.000 claims description 183
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 143
- 230000011987 methylation Effects 0.000 claims description 141
- 238000007069 methylation reaction Methods 0.000 claims description 141
- 102000008138 Bone Morphogenetic Protein 3 Human genes 0.000 claims description 140
- 108010049951 Bone Morphogenetic Protein 3 Proteins 0.000 claims description 140
- 206010001233 Adenoma benign Diseases 0.000 claims description 126
- 230000002441 reversible effect Effects 0.000 claims description 106
- 102100034432 Protein NDRG4 Human genes 0.000 claims description 79
- 230000003321 amplification Effects 0.000 claims description 77
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 77
- 108091029430 CpG site Proteins 0.000 claims description 72
- 238000000034 method Methods 0.000 claims description 72
- 108020004414 DNA Proteins 0.000 claims description 59
- 108090000623 proteins and genes Proteins 0.000 claims description 57
- 238000001514 detection method Methods 0.000 claims description 54
- 238000003753 real-time PCR Methods 0.000 claims description 51
- 239000012472 biological sample Substances 0.000 claims description 49
- 101150006966 bmp3 gene Proteins 0.000 claims description 41
- 238000003752 polymerase chain reaction Methods 0.000 claims description 38
- 101150105104 Kras gene Proteins 0.000 claims description 37
- 239000003153 chemical reaction reagent Substances 0.000 claims description 32
- 108010054147 Hemoglobins Proteins 0.000 claims description 28
- 102000001554 Hemoglobins Human genes 0.000 claims description 28
- 230000035772 mutation Effects 0.000 claims description 25
- 238000009396 hybridization Methods 0.000 claims description 21
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 20
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 16
- 230000000295 complement effect Effects 0.000 claims description 16
- 239000002773 nucleotide Substances 0.000 claims description 16
- 125000003729 nucleotide group Chemical group 0.000 claims description 16
- 239000012634 fragment Substances 0.000 claims description 15
- 108091033319 polynucleotide Proteins 0.000 claims description 15
- 102000040430 polynucleotide Human genes 0.000 claims description 15
- 239000002157 polynucleotide Substances 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 12
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 claims description 12
- 230000002550 fecal effect Effects 0.000 claims description 12
- 102100030708 GTPase KRas Human genes 0.000 claims description 10
- 102200006532 rs112445441 Human genes 0.000 claims description 9
- 102200006531 rs121913529 Human genes 0.000 claims description 9
- 102200006537 rs121913529 Human genes 0.000 claims description 9
- 102200006539 rs121913529 Human genes 0.000 claims description 9
- 102200006538 rs121913530 Human genes 0.000 claims description 9
- 102200006541 rs121913530 Human genes 0.000 claims description 9
- 229940035893 uracil Drugs 0.000 claims description 8
- 229940104302 cytosine Drugs 0.000 claims description 7
- 238000009534 blood test Methods 0.000 claims description 6
- 102200006540 rs121913530 Human genes 0.000 claims description 6
- 102220014328 rs121913535 Human genes 0.000 claims description 6
- 238000003745 diagnosis Methods 0.000 claims description 5
- 230000000984 immunochemical effect Effects 0.000 claims description 5
- 239000002131 composite material Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 108091008146 restriction endonucleases Proteins 0.000 claims description 2
- 108091093088 Amplicon Proteins 0.000 claims 1
- 230000035945 sensitivity Effects 0.000 description 58
- 239000000047 product Substances 0.000 description 42
- 210000001519 tissue Anatomy 0.000 description 29
- 239000000203 mixture Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 238000012360 testing method Methods 0.000 description 24
- 102000039446 nucleic acids Human genes 0.000 description 19
- 108020004707 nucleic acids Proteins 0.000 description 19
- 150000007523 nucleic acids Chemical class 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 230000000052 comparative effect Effects 0.000 description 17
- -1 occupational hazards Substances 0.000 description 15
- 108091029523 CpG island Proteins 0.000 description 14
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 14
- 206010028980 Neoplasm Diseases 0.000 description 14
- 239000006228 supernatant Substances 0.000 description 14
- 108091028043 Nucleic acid sequence Proteins 0.000 description 13
- 238000004925 denaturation Methods 0.000 description 13
- 230000036425 denaturation Effects 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 238000003556 assay Methods 0.000 description 11
- 239000011324 bead Substances 0.000 description 11
- 239000002699 waste material Substances 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 9
- 239000013642 negative control Substances 0.000 description 9
- 230000007170 pathology Effects 0.000 description 9
- 208000037062 Polyps Diseases 0.000 description 8
- 230000003902 lesion Effects 0.000 description 8
- 230000032683 aging Effects 0.000 description 7
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 7
- 238000003908 quality control method Methods 0.000 description 7
- 238000012163 sequencing technique Methods 0.000 description 7
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000002052 colonoscopy Methods 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 6
- 101000756632 Homo sapiens Actin, cytoplasmic 1 Proteins 0.000 description 5
- 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 5
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 5
- 238000007477 logistic regression Methods 0.000 description 5
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 5
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- 101150076800 B2M gene Proteins 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 206010069755 K-ras gene mutation Diseases 0.000 description 4
- 108700009124 Transcription Initiation Site Proteins 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
- 239000003068 molecular probe Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 4
- 238000002579 sigmoidoscopy Methods 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 108020003589 5' Untranslated Regions Proteins 0.000 description 3
- SJQRQOKXQKVJGJ-UHFFFAOYSA-N 5-(2-aminoethylamino)naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(NCCN)=CC=CC2=C1S(O)(=O)=O SJQRQOKXQKVJGJ-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 108010006785 Taq Polymerase Proteins 0.000 description 3
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 3
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 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 3
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 238000007403 mPCR Methods 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 102200006533 rs121913535 Human genes 0.000 description 3
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- RFLVMTUMFYRZCB-UHFFFAOYSA-N 1-methylguanine Chemical compound O=C1N(C)C(N)=NC2=C1N=CN2 RFLVMTUMFYRZCB-UHFFFAOYSA-N 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 2
- OBYNJKLOYWCXEP-UHFFFAOYSA-N 2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]-4-isothiocyanatobenzoate Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC(N=C=S)=CC=C1C([O-])=O OBYNJKLOYWCXEP-UHFFFAOYSA-N 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 description 2
- HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 2
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 description 2
- WQZIDRAQTRIQDX-UHFFFAOYSA-N 6-carboxy-x-rhodamine Chemical compound OC(=O)C1=CC=C(C([O-])=O)C=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 WQZIDRAQTRIQDX-UHFFFAOYSA-N 0.000 description 2
- 101150087690 ACTB gene Proteins 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 238000007400 DNA extraction Methods 0.000 description 2
- XPDXVDYUQZHFPV-UHFFFAOYSA-N Dansyl Chloride Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(Cl)(=O)=O XPDXVDYUQZHFPV-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108700039887 Essential Genes Proteins 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 101000835083 Homo sapiens Tissue factor pathway inhibitor 2 Proteins 0.000 description 2
- 101000803403 Homo sapiens Vimentin Proteins 0.000 description 2
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 2
- 229930010555 Inosine Natural products 0.000 description 2
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 239000012807 PCR reagent Substances 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- 206010039897 Sedation Diseases 0.000 description 2
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 102100035071 Vimentin Human genes 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 238000000137 annealing Methods 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
- 238000003149 assay kit Methods 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
- 239000000090 biomarker Substances 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- VYXSBFYARXAAKO-UHFFFAOYSA-N ethyl 2-[3-(ethylamino)-6-ethylimino-2,7-dimethylxanthen-9-yl]benzoate;hydron;chloride Chemical compound [Cl-].C1=2C=C(C)C(NCC)=CC=2OC2=CC(=[NH+]CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-UHFFFAOYSA-N 0.000 description 2
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229960003786 inosine Drugs 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- DRAVOWXCEBXPTN-UHFFFAOYSA-N isoguanine Chemical compound NC1=NC(=O)NC2=C1NC=N2 DRAVOWXCEBXPTN-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 229940107698 malachite green Drugs 0.000 description 2
- 230000007257 malfunction Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- SHXOKQKTZJXHHR-UHFFFAOYSA-N n,n-diethyl-5-iminobenzo[a]phenoxazin-9-amine;hydrochloride Chemical compound [Cl-].C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=[NH2+])C2=C1 SHXOKQKTZJXHHR-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000036280 sedation Effects 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical class [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 229940075420 xanthine Drugs 0.000 description 2
- CADQNXRGRFJSQY-UOWFLXDJSA-N (2r,3r,4r)-2-fluoro-2,3,4,5-tetrahydroxypentanal Chemical compound OC[C@@H](O)[C@@H](O)[C@@](O)(F)C=O CADQNXRGRFJSQY-UOWFLXDJSA-N 0.000 description 1
- YXTKHLHCVFUPPT-YYFJYKOTSA-N (2s)-2-[[4-[(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid;(1r,2r)-1,2-dimethanidylcyclohexane;5-fluoro-1h-pyrimidine-2,4-dione;oxalic acid;platinum(2+) Chemical compound [Pt+2].OC(=O)C(O)=O.[CH2-][C@@H]1CCCC[C@H]1[CH2-].FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 YXTKHLHCVFUPPT-YYFJYKOTSA-N 0.000 description 1
- GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 1
- SLLFVLKNXABYGI-UHFFFAOYSA-N 1,2,3-benzoxadiazole Chemical compound C1=CC=C2ON=NC2=C1 SLLFVLKNXABYGI-UHFFFAOYSA-N 0.000 description 1
- DUFUXAHBRPMOFG-UHFFFAOYSA-N 1-(4-anilinonaphthalen-1-yl)pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(C1=CC=CC=C11)=CC=C1NC1=CC=CC=C1 DUFUXAHBRPMOFG-UHFFFAOYSA-N 0.000 description 1
- PJXVQPWEQYWHRL-UHFFFAOYSA-N 1-acetyl-4-aminopyrimidin-2-one Chemical compound CC(=O)N1C=CC(N)=NC1=O PJXVQPWEQYWHRL-UHFFFAOYSA-N 0.000 description 1
- ZTTARJIAPRWUHH-UHFFFAOYSA-N 1-isothiocyanatoacridine Chemical compound C1=CC=C2C=C3C(N=C=S)=CC=CC3=NC2=C1 ZTTARJIAPRWUHH-UHFFFAOYSA-N 0.000 description 1
- WJNGQIYEQLPJMN-IOSLPCCCSA-N 1-methylinosine Chemical compound C1=NC=2C(=O)N(C)C=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WJNGQIYEQLPJMN-IOSLPCCCSA-N 0.000 description 1
- VVZRKVYGKNFTRR-UHFFFAOYSA-N 12h-benzo[a]xanthene Chemical compound C1=CC=CC2=C3CC4=CC=CC=C4OC3=CC=C21 VVZRKVYGKNFTRR-UHFFFAOYSA-N 0.000 description 1
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 1
- RUDINRUXCKIXAJ-UHFFFAOYSA-N 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,14,14,14-heptacosafluorotetradecanoic acid Chemical compound OC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F RUDINRUXCKIXAJ-UHFFFAOYSA-N 0.000 description 1
- HLYBTPMYFWWNJN-UHFFFAOYSA-N 2-(2,4-dioxo-1h-pyrimidin-5-yl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CNC(=O)NC1=O HLYBTPMYFWWNJN-UHFFFAOYSA-N 0.000 description 1
- SGAKLDIYNFXTCK-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)methylamino]acetic acid Chemical compound OC(=O)CNCC1=CNC(=O)NC1=O SGAKLDIYNFXTCK-UHFFFAOYSA-N 0.000 description 1
- YSAJFXWTVFGPAX-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetic acid Chemical compound OC(=O)COC1=CNC(=O)NC1=O YSAJFXWTVFGPAX-UHFFFAOYSA-N 0.000 description 1
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 1
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 description 1
- LAXVMANLDGWYJP-UHFFFAOYSA-N 2-amino-5-(2-aminoethyl)naphthalene-1-sulfonic acid Chemical compound NC1=CC=C2C(CCN)=CC=CC2=C1S(O)(=O)=O LAXVMANLDGWYJP-UHFFFAOYSA-N 0.000 description 1
- XMSMHKMPBNTBOD-UHFFFAOYSA-N 2-dimethylamino-6-hydroxypurine Chemical compound N1C(N(C)C)=NC(=O)C2=C1N=CN2 XMSMHKMPBNTBOD-UHFFFAOYSA-N 0.000 description 1
- SMADWRYCYBUIKH-UHFFFAOYSA-N 2-methyl-7h-purin-6-amine Chemical compound CC1=NC(N)=C2NC=NC2=N1 SMADWRYCYBUIKH-UHFFFAOYSA-N 0.000 description 1
- MPPQGYCZBNURDG-UHFFFAOYSA-N 2-propionyl-6-dimethylaminonaphthalene Chemical compound C1=C(N(C)C)C=CC2=CC(C(=O)CC)=CC=C21 MPPQGYCZBNURDG-UHFFFAOYSA-N 0.000 description 1
- BNBQQYFXBLBYJK-UHFFFAOYSA-N 2-pyridin-2-yl-1,3-oxazole Chemical compound C1=COC(C=2N=CC=CC=2)=N1 BNBQQYFXBLBYJK-UHFFFAOYSA-N 0.000 description 1
- CPBJMKMKNCRKQB-UHFFFAOYSA-N 3,3-bis(4-hydroxy-3-methylphenyl)-2-benzofuran-1-one Chemical compound C1=C(O)C(C)=CC(C2(C3=CC=CC=C3C(=O)O2)C=2C=C(C)C(O)=CC=2)=C1 CPBJMKMKNCRKQB-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- IHXWECHPYNPJRR-UHFFFAOYSA-N 3-hydroxycyclobut-2-en-1-one Chemical class OC1=CC(=O)C1 IHXWECHPYNPJRR-UHFFFAOYSA-N 0.000 description 1
- KOLPWZCZXAMXKS-UHFFFAOYSA-N 3-methylcytosine Chemical compound CN1C(N)=CC=NC1=O KOLPWZCZXAMXKS-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- YSCNMFDFYJUPEF-OWOJBTEDSA-N 4,4'-diisothiocyano-trans-stilbene-2,2'-disulfonic acid Chemical compound OS(=O)(=O)C1=CC(N=C=S)=CC=C1\C=C\C1=CC=C(N=C=S)C=C1S(O)(=O)=O YSCNMFDFYJUPEF-OWOJBTEDSA-N 0.000 description 1
- YJCCSLGGODRWKK-NSCUHMNNSA-N 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid Chemical compound OS(=O)(=O)C1=CC(NC(=O)C)=CC=C1\C=C\C1=CC=C(N=C=S)C=C1S(O)(=O)=O YJCCSLGGODRWKK-NSCUHMNNSA-N 0.000 description 1
- OSWZKAVBSQAVFI-UHFFFAOYSA-N 4-[(4-isothiocyanatophenyl)diazenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(N=C=S)C=C1 OSWZKAVBSQAVFI-UHFFFAOYSA-N 0.000 description 1
- UDGUGZTYGWUUSG-UHFFFAOYSA-N 4-[4-[[2,5-dimethoxy-4-[(4-nitrophenyl)diazenyl]phenyl]diazenyl]-n-methylanilino]butanoic acid Chemical compound COC=1C=C(N=NC=2C=CC(=CC=2)N(C)CCCC(O)=O)C(OC)=CC=1N=NC1=CC=C([N+]([O-])=O)C=C1 UDGUGZTYGWUUSG-UHFFFAOYSA-N 0.000 description 1
- UWAUSMGZOHPBJJ-UHFFFAOYSA-N 4-nitro-1,2,3-benzoxadiazole Chemical compound [O-][N+](=O)C1=CC=CC2=C1N=NO2 UWAUSMGZOHPBJJ-UHFFFAOYSA-N 0.000 description 1
- MQJSSLBGAQJNER-UHFFFAOYSA-N 5-(methylaminomethyl)-1h-pyrimidine-2,4-dione Chemical compound CNCC1=CNC(=O)NC1=O MQJSSLBGAQJNER-UHFFFAOYSA-N 0.000 description 1
- WPYRHVXCOQLYLY-UHFFFAOYSA-N 5-[(methoxyamino)methyl]-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CONCC1=CNC(=S)NC1=O WPYRHVXCOQLYLY-UHFFFAOYSA-N 0.000 description 1
- ZWONWYNZSWOYQC-UHFFFAOYSA-N 5-benzamido-3-[[5-[[4-chloro-6-(4-sulfoanilino)-1,3,5-triazin-2-yl]amino]-2-sulfophenyl]diazenyl]-4-hydroxynaphthalene-2,7-disulfonic acid Chemical compound OC1=C(N=NC2=CC(NC3=NC(NC4=CC=C(C=C4)S(O)(=O)=O)=NC(Cl)=N3)=CC=C2S(O)(=O)=O)C(=CC2=C1C(NC(=O)C1=CC=CC=C1)=CC(=C2)S(O)(=O)=O)S(O)(=O)=O ZWONWYNZSWOYQC-UHFFFAOYSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 1
- VKLFQTYNHLDMDP-PNHWDRBUSA-N 5-carboxymethylaminomethyl-2-thiouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=S)NC(=O)C(CNCC(O)=O)=C1 VKLFQTYNHLDMDP-PNHWDRBUSA-N 0.000 description 1
- YERWMQJEYUIJBO-UHFFFAOYSA-N 5-chlorosulfonyl-2-[3-(diethylamino)-6-diethylazaniumylidenexanthen-9-yl]benzenesulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(Cl)(=O)=O)C=C1S([O-])(=O)=O YERWMQJEYUIJBO-UHFFFAOYSA-N 0.000 description 1
- ZFTBZKVVGZNMJR-UHFFFAOYSA-N 5-chlorouracil Chemical compound ClC1=CNC(=O)NC1=O ZFTBZKVVGZNMJR-UHFFFAOYSA-N 0.000 description 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
- AXGKYURDYTXCAG-UHFFFAOYSA-N 5-isothiocyanato-2-[2-(4-isothiocyanato-2-sulfophenyl)ethyl]benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC(N=C=S)=CC=C1CCC1=CC=C(N=C=S)C=C1S(O)(=O)=O AXGKYURDYTXCAG-UHFFFAOYSA-N 0.000 description 1
- KELXHQACBIUYSE-UHFFFAOYSA-N 5-methoxy-1h-pyrimidine-2,4-dione Chemical compound COC1=CNC(=O)NC1=O KELXHQACBIUYSE-UHFFFAOYSA-N 0.000 description 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
- HWQQCFPHXPNXHC-UHFFFAOYSA-N 6-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=CC=2)OC(=O)C1=CC=2NC1=NC(Cl)=NC(Cl)=N1 HWQQCFPHXPNXHC-UHFFFAOYSA-N 0.000 description 1
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 1
- TXSWURLNYUQATR-UHFFFAOYSA-N 6-amino-2-(3-ethenylsulfonylphenyl)-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1C1=CC=CC(S(=O)(=O)C=C)=C1 TXSWURLNYUQATR-UHFFFAOYSA-N 0.000 description 1
- BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 1
- YALJZNKPECPZAS-UHFFFAOYSA-N 7-(diethylamino)-3-(4-isothiocyanatophenyl)-4-methylchromen-2-one Chemical compound O=C1OC2=CC(N(CC)CC)=CC=C2C(C)=C1C1=CC=C(N=C=S)C=C1 YALJZNKPECPZAS-UHFFFAOYSA-N 0.000 description 1
- SGAOZXGJGQEBHA-UHFFFAOYSA-N 82344-98-7 Chemical compound C1CCN2CCCC(C=C3C4(OC(C5=CC(=CC=C54)N=C=S)=O)C4=C5)=C2C1=C3OC4=C1CCCN2CCCC5=C12 SGAOZXGJGQEBHA-UHFFFAOYSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 1
- 241000143060 Americamysis bahia Species 0.000 description 1
- FYEHYMARPSSOBO-UHFFFAOYSA-N Aurin Chemical compound C1=CC(O)=CC=C1C(C=1C=CC(O)=CC=1)=C1C=CC(=O)C=C1 FYEHYMARPSSOBO-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 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 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 102100034330 Chromaffin granule amine transporter Human genes 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 241000958526 Cuon alpinus Species 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- 239000012129 DRAQ7 reagent Substances 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- QTANTQQOYSUMLC-UHFFFAOYSA-O Ethidium cation Chemical compound C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 QTANTQQOYSUMLC-UHFFFAOYSA-O 0.000 description 1
- 206010073306 Exposure to radiation Diseases 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 1
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 1
- 101000641221 Homo sapiens Chromaffin granule amine transporter Proteins 0.000 description 1
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 101100412856 Mus musculus Rhod gene Proteins 0.000 description 1
- SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical compound O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- WDVSHHCDHLJJJR-UHFFFAOYSA-N Proflavine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010057071 Rectal tenesmus Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 1
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 229910052771 Terbium Inorganic materials 0.000 description 1
- 101100242191 Tetraodon nigroviridis rho gene Proteins 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- BGLGAKMTYHWWKW-UHFFFAOYSA-N acridine yellow Chemical compound [H+].[Cl-].CC1=C(N)C=C2N=C(C=C(C(C)=C3)N)C3=CC2=C1 BGLGAKMTYHWWKW-UHFFFAOYSA-N 0.000 description 1
- 150000001251 acridines Chemical class 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 150000001454 anthracenes Chemical class 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 description 1
- 238000013459 approach Methods 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
- 125000003118 aryl group Chemical group 0.000 description 1
- JPIYZTWMUGTEHX-UHFFFAOYSA-N auramine O free base Chemical compound C1=CC(N(C)C)=CC=C1C(=N)C1=CC=C(N(C)C)C=C1 JPIYZTWMUGTEHX-UHFFFAOYSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 208000027503 bloody stool Diseases 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- CZPLANDPABRVHX-UHFFFAOYSA-N cascade blue Chemical compound C=1C2=CC=CC=C2C(NCC)=CC=1C(C=1C=CC(=CC=1)N(CC)CC)=C1C=CC(=[N+](CC)CC)C=C1 CZPLANDPABRVHX-UHFFFAOYSA-N 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 201000002758 colorectal adenoma Diseases 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- 150000004775 coumarins Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000013872 defecation Effects 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000006477 desulfuration reaction Methods 0.000 description 1
- 230000023556 desulfurization Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- RJBIAAZJODIFHR-UHFFFAOYSA-N dihydroxy-imino-sulfanyl-$l^{5}-phosphane Chemical class NP(O)(O)=S RJBIAAZJODIFHR-UHFFFAOYSA-N 0.000 description 1
- OVTCUIZCVUGJHS-UHFFFAOYSA-N dipyrrin Chemical compound C=1C=CNC=1C=C1C=CC=N1 OVTCUIZCVUGJHS-UHFFFAOYSA-N 0.000 description 1
- OOYIOIOOWUGAHD-UHFFFAOYSA-L disodium;2',4',5',7'-tetrabromo-4,5,6,7-tetrachloro-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(Br)=C([O-])C(Br)=C1OC1=C(Br)C([O-])=C(Br)C=C21 OOYIOIOOWUGAHD-UHFFFAOYSA-L 0.000 description 1
- RAGZEDHHTPQLAI-UHFFFAOYSA-L disodium;2',4',5',7'-tetraiodo-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(I)=C([O-])C(I)=C1OC1=C(I)C([O-])=C(I)C=C21 RAGZEDHHTPQLAI-UHFFFAOYSA-L 0.000 description 1
- KPBGWWXVWRSIAY-UHFFFAOYSA-L disodium;2',4',5',7'-tetraiodo-6-isothiocyanato-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C2=CC=C(N=C=S)C=C2C21C1=CC(I)=C([O-])C(I)=C1OC1=C(I)C([O-])=C(I)C=C21 KPBGWWXVWRSIAY-UHFFFAOYSA-L 0.000 description 1
- 210000004921 distal colon Anatomy 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000000572 ellipsometry Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- XHXYXYGSUXANME-UHFFFAOYSA-N eosin 5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC(Br)=C(O)C(Br)=C1OC1=C(Br)C(O)=C(Br)C=C21 XHXYXYGSUXANME-UHFFFAOYSA-N 0.000 description 1
- IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 description 1
- 229940011411 erythrosine Drugs 0.000 description 1
- 239000004174 erythrosine Substances 0.000 description 1
- 235000012732 erythrosine Nutrition 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000000695 excitation spectrum Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 1
- JYEFSHLLTQIXIO-SMNQTINBSA-N folfiri regimen Chemical compound FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 JYEFSHLLTQIXIO-SMNQTINBSA-N 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 206010022694 intestinal perforation Diseases 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- FDZZZRQASAIRJF-UHFFFAOYSA-M malachite green Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC=CC=1)=C1C=CC(=[N+](C)C)C=C1 FDZZZRQASAIRJF-UHFFFAOYSA-M 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 210000001809 melena Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- DZVCFNFOPIZQKX-LTHRDKTGSA-M merocyanine Chemical compound [Na+].O=C1N(CCCC)C(=O)N(CCCC)C(=O)C1=C\C=C\C=C/1N(CCCS([O-])(=O)=O)C2=CC=CC=C2O\1 DZVCFNFOPIZQKX-LTHRDKTGSA-M 0.000 description 1
- IZAGSTRIDUNNOY-UHFFFAOYSA-N methyl 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetate Chemical compound COC(=O)COC1=CNC(=O)NC1=O IZAGSTRIDUNNOY-UHFFFAOYSA-N 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- XJVXMWNLQRTRGH-UHFFFAOYSA-N n-(3-methylbut-3-enyl)-2-methylsulfanyl-7h-purin-6-amine Chemical compound CSC1=NC(NCCC(C)=C)=C2NC=NC2=N1 XJVXMWNLQRTRGH-UHFFFAOYSA-N 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- VOFUROIFQGPCGE-UHFFFAOYSA-N nile red Chemical compound C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=O)C2=C1 VOFUROIFQGPCGE-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- GHTWDWCFRFTBRB-UHFFFAOYSA-M oxazine-170 Chemical compound [O-]Cl(=O)(=O)=O.N1=C2C3=CC=CC=C3C(NCC)=CC2=[O+]C2=C1C=C(C)C(N(C)CC)=C2 GHTWDWCFRFTBRB-UHFFFAOYSA-M 0.000 description 1
- 150000004893 oxazines Chemical class 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- AFAIELJLZYUNPW-UHFFFAOYSA-N pararosaniline free base Chemical compound C1=CC(N)=CC=C1C(C=1C=CC(N)=CC=1)=C1C=CC(=N)C=C1 AFAIELJLZYUNPW-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- JZRYQZJSTWVBBD-UHFFFAOYSA-N pentaporphyrin i Chemical compound N1C(C=C2NC(=CC3=NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 JZRYQZJSTWVBBD-UHFFFAOYSA-N 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 150000008299 phosphorodiamidates Chemical class 0.000 description 1
- 230000001443 photoexcitation Effects 0.000 description 1
- 238000005375 photometry Methods 0.000 description 1
- ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 1
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229960000286 proflavine Drugs 0.000 description 1
- 230000000135 prohibitive effect Effects 0.000 description 1
- AJMSJNPWXJCWOK-UHFFFAOYSA-N pyren-1-yl butanoate Chemical compound C1=C2C(OC(=O)CCC)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 AJMSJNPWXJCWOK-UHFFFAOYSA-N 0.000 description 1
- 150000003220 pyrenes Chemical class 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- MYFATKRONKHHQL-UHFFFAOYSA-N rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C2C=CC(=[NH2+])C=C2OC2=CC(N)=CC=C21 MYFATKRONKHHQL-UHFFFAOYSA-N 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- COIVODZMVVUETJ-UHFFFAOYSA-N sulforhodamine 101 Chemical compound OS(=O)(=O)C1=CC(S([O-])(=O)=O)=CC=C1C1=C(C=C2C3=C4CCCN3CCC2)C4=[O+]C2=C1C=C1CCCN3CCCC2=C13 COIVODZMVVUETJ-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000012271 tenesmus Diseases 0.000 description 1
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 125000001834 xanthenyl group Chemical class C1=CC=CC=2OC3=CC=CC=C3C(C12)* 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
-
- 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
- G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
- G01N33/721—Haemoglobin
-
- 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
- C12Q2561/00—Nucleic acid detection characterised by assay method
- C12Q2561/113—Real time assay
-
- 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
- C12Q2600/154—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
- C12Q2600/156—Polymorphic or mutational 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
- C12Q2600/16—Primer sets for multiplex assays
-
- 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
- C12Q2600/166—Oligonucleotides used as internal standards, controls or normalisation probes
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hospice & Palliative Care (AREA)
- General Engineering & Computer Science (AREA)
- Oncology (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810502359.7A CN108660209B (zh) | 2018-05-23 | 2018-05-23 | 基于bmp3基因甲基化制备结直肠癌早期检测的产品 |
| CN201810502387.9 | 2018-05-23 | ||
| CN201810502387.9A CN108676878B (zh) | 2018-05-23 | 2018-05-23 | 检测ndrg4基因甲基化位点的产品在制备结直肠癌早期检测的产品的用途 |
| CN201810502359.7 | 2018-05-23 | ||
| PCT/US2019/033831 WO2019226942A1 (en) | 2018-05-23 | 2019-05-23 | The kit for screening colorectal cancer and advanced adenoma and its application |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2021526370A JP2021526370A (ja) | 2021-10-07 |
| JPWO2019226942A5 JPWO2019226942A5 (https=) | 2022-05-30 |
| JP2021526370A5 JP2021526370A5 (https=) | 2022-05-30 |
| JP7637509B2 true JP7637509B2 (ja) | 2025-02-28 |
Family
ID=68617194
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020564893A Active JP7637509B2 (ja) | 2018-05-23 | 2019-05-23 | 大腸がんおよび進行腺腫をスクリーニングするためのキットおよびその応用 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20210207221A1 (https=) |
| EP (1) | EP3797112A4 (https=) |
| JP (1) | JP7637509B2 (https=) |
| KR (1) | KR20210035094A (https=) |
| CN (1) | CN112752763B (https=) |
| AU (1) | AU2019275073A1 (https=) |
| BR (1) | BR112020023274A2 (https=) |
| CA (1) | CA3098028A1 (https=) |
| SG (1) | SG11202010208YA (https=) |
| WO (1) | WO2019226942A1 (https=) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113699237A (zh) * | 2020-07-29 | 2021-11-26 | 上海吉凯医学检验所有限公司 | 一种检测早期结直肠癌和腺瘤的dna甲基化标志物的试剂盒 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104975110A (zh) | 2015-06-02 | 2015-10-14 | 浙江诺辉生物技术有限公司 | 用于检测生物样本中bmp3和ndrg4甲基化水平的引物和探针 |
| CN106399570A (zh) | 2016-11-30 | 2017-02-15 | 杭州诺辉健康科技有限公司 | 用于早期结直肠癌辅助诊断的试剂盒及其使用方法和检测系统 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5541308A (en) * | 1986-11-24 | 1996-07-30 | Gen-Probe Incorporated | Nucleic acid probes for detection and/or quantitation of non-viral organisms |
| EP1942197A1 (de) * | 2000-09-01 | 2008-07-09 | Epigenomics AG | Verfahren zur Bestimmung des Methylierungsgrades von bestimmten Cytosinen in genomischer DNA im Sequenzkontext 5'-CpG-3' |
| DE10112515B4 (de) * | 2001-03-09 | 2004-02-12 | Epigenomics Ag | Verfahren zum Nachweis von Cytosin-Methylierungsmustern mit hoher Sensitivität |
| CN103649298A (zh) * | 2011-05-12 | 2014-03-19 | 精密科学公司 | 核酸的分离 |
| WO2013142545A1 (en) * | 2012-03-20 | 2013-09-26 | Exact Sciences Corporation | Marker panel for detecting cancer |
| EP4234722A3 (en) * | 2014-03-31 | 2023-09-20 | Mayo Foundation for Medical Education and Research | Detecting colorectal neoplasm |
| WO2016094839A2 (en) * | 2014-12-12 | 2016-06-16 | Exact Sciences Corporation | Compositions and methods for performing methylation detection assays |
| ES2879964T3 (es) * | 2014-12-12 | 2021-11-23 | Exact Sciences Dev Co Llc | Composiciones y métodos para realizar ensayos de detección de metilación |
| AU2016343937B2 (en) * | 2015-10-30 | 2023-01-19 | Exact Sciences Corporation | Multiplex amplification detection assay and isolation and detection of DNA from plasma |
| WO2018087129A1 (en) * | 2016-11-08 | 2018-05-17 | Region Nordjylland, Aalborg University Hospital | Colorectal cancer methylation markers |
-
2019
- 2019-05-23 EP EP19806858.7A patent/EP3797112A4/en not_active Withdrawn
- 2019-05-23 CN CN201980033966.6A patent/CN112752763B/zh active Active
- 2019-05-23 BR BR112020023274-2A patent/BR112020023274A2/pt unknown
- 2019-05-23 JP JP2020564893A patent/JP7637509B2/ja active Active
- 2019-05-23 SG SG11202010208YA patent/SG11202010208YA/en unknown
- 2019-05-23 AU AU2019275073A patent/AU2019275073A1/en not_active Abandoned
- 2019-05-23 US US17/057,227 patent/US20210207221A1/en not_active Abandoned
- 2019-05-23 WO PCT/US2019/033831 patent/WO2019226942A1/en not_active Ceased
- 2019-05-23 KR KR1020207037127A patent/KR20210035094A/ko active Pending
- 2019-05-23 CA CA3098028A patent/CA3098028A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104975110A (zh) | 2015-06-02 | 2015-10-14 | 浙江诺辉生物技术有限公司 | 用于检测生物样本中bmp3和ndrg4甲基化水平的引物和探针 |
| CN106399570A (zh) | 2016-11-30 | 2017-02-15 | 杭州诺辉健康科技有限公司 | 用于早期结直肠癌辅助诊断的试剂盒及其使用方法和检测系统 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019226942A1 (en) | 2019-11-28 |
| EP3797112A1 (en) | 2021-03-31 |
| US20210207221A1 (en) | 2021-07-08 |
| KR20210035094A (ko) | 2021-03-31 |
| AU2019275073A8 (en) | 2020-12-10 |
| JP2021526370A (ja) | 2021-10-07 |
| BR112020023274A2 (pt) | 2021-02-23 |
| CN112752763B (zh) | 2025-01-03 |
| SG11202010208YA (en) | 2020-11-27 |
| CA3098028A1 (en) | 2019-11-28 |
| EP3797112A4 (en) | 2022-03-23 |
| CN112752763A (zh) | 2021-05-04 |
| AU2019275073A1 (en) | 2020-11-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11021758B2 (en) | Methods for detecting gene dysregulation by intragenic differential expression | |
| EP4421489A2 (en) | Diagnostic applications using nucleic acid fragments | |
| CN115354076A (zh) | 通过使用平均循环阈值的基因内差异表达(ide)检测基因融合 | |
| US12584165B2 (en) | Method for identifying one or more mutations in a hotspot mutation sequence | |
| US20220267859A1 (en) | Use of detection reagent for detecting methylation of genes associated with colorectal cancer, and kit | |
| US20200340057A1 (en) | Dna targets as tissue-specific methylation markers | |
| US20200165671A1 (en) | Detecting tissue-specific dna | |
| JP7637509B2 (ja) | 大腸がんおよび進行腺腫をスクリーニングするためのキットおよびその応用 | |
| CN105705655A (zh) | 用于对nras和braf核酸进行多重分析的组合物及方法 | |
| RU2812023C2 (ru) | Набор для скрининга на рак прямой и ободочной кишки и прогрессирующей аденомы и его применение | |
| HK40042105B (zh) | 筛查结直肠癌和晚期腺瘤的试剂盒及其应用 | |
| HK40042105A (en) | The kit for screening colorectal cancer and advanced adenoma and its application | |
| HK40115228A (en) | Diagnostic applications using nucleic acid fragments | |
| CN120272593A (zh) | 用于诊断胃癌的甲基化生物标记物及其应用 | |
| Gómez | P1. 02-027 A Comparative Analysis of Different Cytological Samples for the Assessment of ALK Gene Rearrangements in NSCLC Patients | |
| CN109207597A (zh) | 一种用于检测头颈癌变异程度的检测套组 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220520 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220520 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230523 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230814 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231020 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20240109 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240508 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20240621 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20241001 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20241004 |
|
| 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: 20250128 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20250217 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7637509 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |