JP2018528441A - 非小細胞肺癌診断用タンパク質バイオマーカーパネル及びこれを用いた非小細胞肺癌診断方法 - Google Patents
非小細胞肺癌診断用タンパク質バイオマーカーパネル及びこれを用いた非小細胞肺癌診断方法 Download PDFInfo
- Publication number
- JP2018528441A JP2018528441A JP2018533586A JP2018533586A JP2018528441A JP 2018528441 A JP2018528441 A JP 2018528441A JP 2018533586 A JP2018533586 A JP 2018533586A JP 2018533586 A JP2018533586 A JP 2018533586A JP 2018528441 A JP2018528441 A JP 2018528441A
- Authority
- JP
- Japan
- Prior art keywords
- biomarker
- lung cancer
- small cell
- cell lung
- sample
- 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.)
- Granted
Links
- 239000000090 biomarker Substances 0.000 title claims abstract description 299
- 208000002154 non-small cell lung carcinoma Diseases 0.000 title claims abstract description 120
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 title claims abstract description 117
- 108090000623 proteins and genes Proteins 0.000 title claims description 97
- 102000004169 proteins and genes Human genes 0.000 title claims description 88
- 238000002405 diagnostic procedure Methods 0.000 title description 8
- 238000000034 method Methods 0.000 claims abstract description 185
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 47
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 43
- 201000005202 lung cancer Diseases 0.000 claims abstract description 43
- 108091023037 Aptamer Proteins 0.000 claims description 139
- 239000003153 chemical reaction reagent Substances 0.000 claims description 49
- 239000012472 biological sample Substances 0.000 claims description 43
- 238000003556 assay Methods 0.000 claims description 39
- 238000005259 measurement Methods 0.000 claims description 28
- 210000002966 serum Anatomy 0.000 claims description 26
- 238000004458 analytical method Methods 0.000 claims description 19
- 230000002685 pulmonary effect Effects 0.000 claims description 13
- 210000004369 blood Anatomy 0.000 claims description 10
- 239000008280 blood Substances 0.000 claims description 10
- 230000003211 malignant effect Effects 0.000 claims description 9
- 108010074051 C-Reactive Protein Proteins 0.000 claims description 8
- 102100032752 C-reactive protein Human genes 0.000 claims description 8
- 102100036369 Carbonic anhydrase 6 Human genes 0.000 claims description 8
- 102000004318 Matrilysin Human genes 0.000 claims description 8
- 108090000855 Matrilysin Proteins 0.000 claims description 8
- 108010019521 carbonic anhydrase VI Proteins 0.000 claims description 8
- 210000002381 plasma Anatomy 0.000 claims description 8
- 102000005962 receptors Human genes 0.000 claims description 8
- 108020003175 receptors Proteins 0.000 claims description 8
- 238000002493 microarray Methods 0.000 claims description 7
- 102100032528 C-type lectin domain family 11 member A Human genes 0.000 claims description 5
- 101710167766 C-type lectin domain family 11 member A Proteins 0.000 claims description 5
- 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 claims description 4
- 102000008929 Complement component C9 Human genes 0.000 claims description 4
- 108050000891 Complement component C9 Proteins 0.000 claims description 4
- 102000001301 EGF receptor Human genes 0.000 claims description 4
- 108060006698 EGF receptor Proteins 0.000 claims description 4
- 101000678026 Homo sapiens Alpha-1-antichymotrypsin Proteins 0.000 claims description 4
- 108020004711 Nucleic Acid Probes Proteins 0.000 claims description 4
- 238000005462 in vivo assay Methods 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000002853 nucleic acid probe Substances 0.000 claims description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 4
- 238000003753 real-time PCR Methods 0.000 claims description 4
- 238000007619 statistical method Methods 0.000 claims description 4
- 238000012706 support-vector machine Methods 0.000 claims description 3
- 238000007477 logistic regression Methods 0.000 claims description 2
- 239000011325 microbead Substances 0.000 claims description 2
- 238000007637 random forest analysis Methods 0.000 claims description 2
- 239000000523 sample Substances 0.000 description 123
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 67
- 201000010099 disease Diseases 0.000 description 62
- 210000001519 tissue Anatomy 0.000 description 57
- 238000012360 testing method Methods 0.000 description 53
- 210000004027 cell Anatomy 0.000 description 50
- 239000003550 marker Substances 0.000 description 50
- 238000011282 treatment Methods 0.000 description 48
- 230000014509 gene expression Effects 0.000 description 47
- 238000001514 detection method Methods 0.000 description 45
- 239000007787 solid Substances 0.000 description 34
- 102000039446 nucleic acids Human genes 0.000 description 32
- 108020004707 nucleic acids Proteins 0.000 description 32
- 150000007523 nucleic acids Chemical class 0.000 description 32
- 239000000243 solution Substances 0.000 description 32
- 206010028980 Neoplasm Diseases 0.000 description 30
- 230000008569 process Effects 0.000 description 30
- 239000012634 fragment Substances 0.000 description 29
- 239000000203 mixture Substances 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 238000012216 screening Methods 0.000 description 26
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 24
- 201000011510 cancer Diseases 0.000 description 24
- 239000012491 analyte Substances 0.000 description 20
- 238000009739 binding Methods 0.000 description 19
- 238000003384 imaging method Methods 0.000 description 19
- 230000027455 binding Effects 0.000 description 18
- 238000003745 diagnosis Methods 0.000 description 18
- 230000035945 sensitivity Effects 0.000 description 18
- 238000010186 staining Methods 0.000 description 18
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 17
- 239000000463 material Substances 0.000 description 17
- 239000000126 substance Substances 0.000 description 17
- 238000012549 training Methods 0.000 description 16
- 238000005406 washing Methods 0.000 description 16
- 239000000872 buffer Substances 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 15
- 108091034117 Oligonucleotide Proteins 0.000 description 14
- 238000012300 Sequence Analysis Methods 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 229920001817 Agar Polymers 0.000 description 12
- 239000008272 agar Substances 0.000 description 12
- 229960002685 biotin Drugs 0.000 description 12
- 235000020958 biotin Nutrition 0.000 description 12
- 239000011616 biotin Substances 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 12
- 229940088598 enzyme Drugs 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 206010056342 Pulmonary mass Diseases 0.000 description 11
- 150000001413 amino acids Chemical group 0.000 description 11
- 108010036226 antigen CYFRA21.1 Proteins 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 230000001419 dependent effect Effects 0.000 description 11
- 125000003729 nucleotide group Chemical group 0.000 description 11
- 238000001356 surgical procedure Methods 0.000 description 11
- 230000006870 function Effects 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000002380 cytological effect Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000000975 dye Substances 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 239000000834 fixative Substances 0.000 description 9
- 238000003018 immunoassay Methods 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 210000004072 lung Anatomy 0.000 description 9
- 108020004999 messenger RNA Proteins 0.000 description 9
- 108091070501 miRNA Proteins 0.000 description 9
- 239000002679 microRNA Substances 0.000 description 9
- 238000003199 nucleic acid amplification method Methods 0.000 description 9
- 230000000391 smoking effect Effects 0.000 description 9
- 206010054107 Nodule Diseases 0.000 description 8
- 230000002159 abnormal effect Effects 0.000 description 8
- -1 carboxy, amino Chemical group 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 239000011521 glass Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 238000004949 mass spectrometry Methods 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- 239000000107 tumor biomarker Substances 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- 230000003321 amplification Effects 0.000 description 7
- 230000000903 blocking effect Effects 0.000 description 7
- 238000004422 calculation algorithm Methods 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000004005 microsphere Substances 0.000 description 7
- 239000002773 nucleotide Substances 0.000 description 7
- 239000008188 pellet Substances 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 239000008096 xylene Substances 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000035699 permeability Effects 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000001993 wax Substances 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- 238000002820 assay format Methods 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 210000000038 chest Anatomy 0.000 description 5
- 239000002872 contrast media Substances 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000003795 desorption Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000005315 distribution function Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000002372 labelling Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 239000012488 sample solution Substances 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- WHVNXSBKJGAXKU-UHFFFAOYSA-N Alexa Fluor 532 Chemical compound [H+].[H+].CC1(C)C(C)NC(C(=C2OC3=C(C=4C(C(C(C)N=4)(C)C)=CC3=3)S([O-])(=O)=O)S([O-])(=O)=O)=C1C=C2C=3C(C=C1)=CC=C1C(=O)ON1C(=O)CCC1=O WHVNXSBKJGAXKU-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 108010067770 Endopeptidase K Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 4
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 108010090804 Streptavidin Proteins 0.000 description 4
- 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 4
- 238000001574 biopsy Methods 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002591 computed tomography Methods 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 4
- 239000012216 imaging agent Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000000877 morphologic effect Effects 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 238000002600 positron emission tomography Methods 0.000 description 4
- 238000004393 prognosis Methods 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000012099 Alexa Fluor family Substances 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 238000011529 RT qPCR Methods 0.000 description 3
- 206010041067 Small cell lung cancer Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 238000001854 atmospheric pressure photoionisation mass spectrometry Methods 0.000 description 3
- 239000000091 biomarker candidate Substances 0.000 description 3
- 238000004113 cell culture Methods 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
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 238000002059 diagnostic imaging Methods 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 238000013399 early diagnosis Methods 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000012744 immunostaining Methods 0.000 description 3
- 238000000370 laser capture micro-dissection Methods 0.000 description 3
- 208000037841 lung tumor Diseases 0.000 description 3
- 238000002595 magnetic resonance imaging Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000005374 membrane filtration Methods 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 239000002096 quantum dot Substances 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000012898 sample dilution Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000002603 single-photon emission computed tomography Methods 0.000 description 3
- 208000000587 small cell lung carcinoma Diseases 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 210000003802 sputum Anatomy 0.000 description 3
- 208000024794 sputum Diseases 0.000 description 3
- 238000013179 statistical model Methods 0.000 description 3
- 229940056501 technetium 99m Drugs 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 239000012114 Alexa Fluor 647 Substances 0.000 description 2
- 239000012116 Alexa Fluor 680 Substances 0.000 description 2
- 102000008102 Ankyrins Human genes 0.000 description 2
- 108010049777 Ankyrins Proteins 0.000 description 2
- 108010031480 Artificial Receptors Proteins 0.000 description 2
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 238000004252 FT/ICR mass spectrometry Methods 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 102000013460 Malate Dehydrogenase Human genes 0.000 description 2
- 108010026217 Malate Dehydrogenase Proteins 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000029918 bioluminescence Effects 0.000 description 2
- 238000005415 bioluminescence Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- 238000013276 bronchoscopy Methods 0.000 description 2
- 230000001680 brushing effect Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000003392 chemiluminescence resonance energy transfer Methods 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 102000003675 cytokine receptors Human genes 0.000 description 2
- 108010057085 cytokine receptors Proteins 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000007418 data mining Methods 0.000 description 2
- 238000004042 decolorization Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229960000633 dextran sulfate Drugs 0.000 description 2
- 230000009274 differential gene expression Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000012149 elution buffer Substances 0.000 description 2
- 230000007515 enzymatic degradation Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- YCKRFDGAMUMZLT-BJUDXGSMSA-N fluorine-18 atom Chemical compound [18F] YCKRFDGAMUMZLT-BJUDXGSMSA-N 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000011223 gene expression profiling Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 229960000789 guanidine hydrochloride Drugs 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 108091008039 hormone receptors Proteins 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000003100 immobilizing effect Effects 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 238000011503 in vivo imaging Methods 0.000 description 2
- 229940055742 indium-111 Drugs 0.000 description 2
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000001001 laser micro-dissection Methods 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000029226 lipidation Effects 0.000 description 2
- 238000011866 long-term treatment Methods 0.000 description 2
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000001531 micro-dissection Methods 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 238000012634 optical imaging Methods 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 238000011176 pooling Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229940079877 pyrogallol Drugs 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000005096 rolling process Methods 0.000 description 2
- 239000000565 sealant Substances 0.000 description 2
- 238000001004 secondary ion mass spectrometry Methods 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000000779 smoke Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 238000003260 vortexing Methods 0.000 description 2
- DTLVBHCSSNJCMJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoate Chemical compound S1CC2NC(=O)NC2C1CCCCC(=O)NCCOCCOCCOCCOCCC(=O)ON1C(=O)CCC1=O DTLVBHCSSNJCMJ-UHFFFAOYSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- CBXRMKZFYQISIV-UHFFFAOYSA-N 1-n,1-n,1-n',1-n',2-n,2-n,2-n',2-n'-octamethylethene-1,1,2,2-tetramine Chemical group CN(C)C(N(C)C)=C(N(C)C)N(C)C CBXRMKZFYQISIV-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- INEWUCPYEUEQTN-UHFFFAOYSA-N 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(O)CNC1CCCCC1 INEWUCPYEUEQTN-UHFFFAOYSA-N 0.000 description 1
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
- MPVDXIMFBOLMNW-ISLYRVAYSA-N 7-hydroxy-8-[(E)-phenyldiazenyl]naphthalene-1,3-disulfonic acid Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1\N=N\C1=CC=CC=C1 MPVDXIMFBOLMNW-ISLYRVAYSA-N 0.000 description 1
- 240000007241 Agrostis stolonifera Species 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 239000012117 Alexa Fluor 700 Substances 0.000 description 1
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical compound [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 238000010207 Bayesian analysis Methods 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- BVTJGGGYKAMDBN-UHFFFAOYSA-N Dioxetane Chemical class C1COO1 BVTJGGGYKAMDBN-UHFFFAOYSA-N 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 108010015133 Galactose oxidase Proteins 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
- 102100022624 Glucoamylase Human genes 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 102100033420 Keratin, type I cytoskeletal 19 Human genes 0.000 description 1
- 108010066302 Keratin-19 Proteins 0.000 description 1
- 238000007397 LAMP assay Methods 0.000 description 1
- 238000012773 Laboratory assay Methods 0.000 description 1
- 108010023244 Lactoperoxidase Proteins 0.000 description 1
- 102000045576 Lactoperoxidases Human genes 0.000 description 1
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 238000007476 Maximum Likelihood Methods 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- QJGQUHMNIGDVPM-BJUDXGSMSA-N Nitrogen-13 Chemical compound [13N] QJGQUHMNIGDVPM-BJUDXGSMSA-N 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 206010073310 Occupational exposures Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002535 Polyethylene Glycol 1500 Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 108010066717 Q beta Replicase Proteins 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 206010066902 Surgical failure Diseases 0.000 description 1
- 108091046915 Threose nucleic acid Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 108010079337 Tissue Polypeptide Antigen Proteins 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108010092464 Urate Oxidase Proteins 0.000 description 1
- 108010046334 Urease Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 108010093894 Xanthine oxidase Proteins 0.000 description 1
- 102100033220 Xanthine oxidase Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical class C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000003915 air pollution Methods 0.000 description 1
- 108010004469 allophycocyanin Proteins 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 210000004381 amniotic fluid Anatomy 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 239000010425 asbestos Substances 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 238000004630 atomic force microscopy Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 210000003969 blast cell Anatomy 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229920005549 butyl rubber Polymers 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- OKTJSMMVPCPJKN-BJUDXGSMSA-N carbon-11 Chemical compound [11C] OKTJSMMVPCPJKN-BJUDXGSMSA-N 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- VYXSBFYARXAAKO-WTKGSRSZSA-N chembl402140 Chemical compound Cl.C1=2C=C(C)C(NCC)=CC=2OC2=C\C(=N/CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-WTKGSRSZSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical class CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 1
- 238000011976 chest X-ray Methods 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000013170 computed tomography imaging Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003583 cytomorphological effect Effects 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
- 238000013480 data collection Methods 0.000 description 1
- 238000003066 decision tree Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000007435 diagnostic evaluation Methods 0.000 description 1
- 239000012502 diagnostic product Substances 0.000 description 1
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 238000011209 electrochromatography Methods 0.000 description 1
- 230000005264 electron capture Effects 0.000 description 1
- 238000002101 electrospray ionisation tandem mass spectrometry Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 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
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000005562 fading Methods 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 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 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000005337 ground glass Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000005040 ion trap Methods 0.000 description 1
- 238000000534 ion trap mass spectrometry Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 229940057428 lactoperoxidase Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960001614 levamisole Drugs 0.000 description 1
- 238000007834 ligase chain reaction Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- KNJDBYZZKAZQNG-UHFFFAOYSA-N lucigenin Chemical compound [O-][N+]([O-])=O.[O-][N+]([O-])=O.C12=CC=CC=C2[N+](C)=C(C=CC=C2)C2=C1C1=C(C=CC=C2)C2=[N+](C)C2=CC=CC=C12 KNJDBYZZKAZQNG-UHFFFAOYSA-N 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 210000004880 lymph fluid Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 108010029942 microperoxidase Proteins 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000004848 nephelometry Methods 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000000101 novel biomarker Substances 0.000 description 1
- 108091008104 nucleic acid aptamers Proteins 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 231100000675 occupational exposure Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 238000004223 overdiagnosis Methods 0.000 description 1
- QVGXLLKOCUKJST-BJUDXGSMSA-N oxygen-15 atom Chemical compound [15O] QVGXLLKOCUKJST-BJUDXGSMSA-N 0.000 description 1
- 238000009595 pap smear Methods 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000863 peptide conjugate Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 210000004910 pleural fluid Anatomy 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000011116 polymethylpentene Substances 0.000 description 1
- 229920000306 polymethylpentene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 238000010384 proximity ligation assay Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000005173 quadrupole mass spectroscopy Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 238000010833 quantitative mass spectrometry Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 229910052704 radon Inorganic materials 0.000 description 1
- SYUHGPGVQRZVTB-UHFFFAOYSA-N radon atom Chemical compound [Rn] SYUHGPGVQRZVTB-UHFFFAOYSA-N 0.000 description 1
- 229910052761 rare earth metal Inorganic materials 0.000 description 1
- 150000002910 rare earth metals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 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 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000004574 scanning tunneling microscopy Methods 0.000 description 1
- 238000013077 scoring method Methods 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000018528 secretion by tissue Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 150000003376 silicon Chemical class 0.000 description 1
- 238000002922 simulated annealing Methods 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229920003048 styrene butadiene rubber Polymers 0.000 description 1
- 238000010897 surface acoustic wave method Methods 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 238000000756 surface-enhanced laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
- VUYXVWGKCKTUMF-UHFFFAOYSA-N tetratriacontaethylene glycol monomethyl ether Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO VUYXVWGKCKTUMF-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- XLYOFNOQVPJJNP-OUBTZVSYSA-N water-17o Chemical compound [17OH2] XLYOFNOQVPJJNP-OUBTZVSYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Classifications
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57423—Specifically defined cancers of lung
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4737—C-reactive protein
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/7056—Selectin superfamily, e.g. LAM-1, GlyCAM, ELAM-1, PADGEM
- G01N2333/70564—Selectins, e.g. CD62
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/988—Lyases (4.), e.g. aldolases, heparinase, enolases, fumarase
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Physics & Mathematics (AREA)
- Hospice & Palliative Care (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
【選択図】図1
Description
前記ヒトは、アジア人であり得る。
前記ヒトは、喫煙者であり得る。
前記ヒトは、悪性肺結節を持ち得る。
前記パネルは、補体成分C9、炭酸脱水酵素(carbonic anhydrase)6(CA6)、C-反応性タンパク質(CRP)、表皮成長因子受容体1(EGFR1)、マトリックスメタロプロテアーゼ7(MMP7)、アルファ(α)1-アンチプロテアーゼ(SERPINA3)及び幹細胞成長因子受容体(KIT)の測定値を有することができる。
前記ヒトは、アジア人であり得る。
前記ヒトは、喫煙者であり得る。
前記ヒトは、悪性肺結節を持ち得る。
(バイオマーカーの例示的用途)
(アプタマー基盤の検定法を用いてバイオマーカー値を決定)
(免疫検定法を用いたバイオマーカー値の測定)
(遺伝子発現プロフィーリングを用いたバイオマーカー値の測定)
(生体内の分子映像技術を用いたバイオマーカーの検出)
(組織学的/細胞学的方法を用いたバイオマーカー値の測定)
(質量分析方法を用いたバイオマーカー値の測定)
(近接結合検定法を用いたバイオマーカー値の測定)
(バイオマーカーの分類及び疾病スコアの計算)
と記載され、
値を持つn個のマーカーを観察できる総単純ベイズ確率は
と記載され、ここで個人xiはRFU又はログRFUで測定されたバイオマーカーレベルである。未知に対する分類指定は、同一の測定値に対して疾病を患わない可能性(対照群)
と比較し、測定値
のある疾病を患う可能性
及び
は、測定されたRFU値xi、即ちμd及びσdを用いたp(xi|d)に対して類似の式を有するRFU値で正規又はログ-正規分布と仮定される。前記モデルのパラメーター化のためには、トレーニングデータから各クラス-依存性pdfに対する2つのパラメーター、平均μ及び分散σ2推定を行う必要がある。これは、例えば、最大尤度推定、最小自乗及び当業者に公知となった任意の方法を含む多数の方法で達成され得る。μとσに対する正規分布を前記に定義された対数尤度比に代入すれば、下記の通りである。
の値で定義され、これら2つの経験累積分布関数(empiricalcumulative distribution function, cdf)間の最大の差である。n番の観察XiセットAに対する経験的累積分布関数は次の通りに定義され、ここでIXixはXi<xである場合、1と同一であり、そうでなければ0と同一の表示関数(indicator function)である。その意味上、この値は0と1との間にあり、ここでKS-距離1は経験的分布が重複しないことを表す。
(臨床サンプルの獲得)
(候補バイオマーカーの測定)
(バイオマーカー値の調整(calibration))
(非小細胞肺癌のためのバイオマーカーの選定)
(単純ベイズ分類器の確立)
事後確率(posterior)=尤度(likelihood)×事前確率(prior)/証拠(evidence)
尤度比率(likelihood ratio)=P(d|x)/P(c|x)=p(d)/(1−p(d)xPi(p(x|d)/p(x|c))
対数尤度比は、疾病の状態を区分するための単一スコアで用いられる。
[実施形態]
(実施形態1:サンプルの製造)
(実施形態2:多重アプタマー検定法によるサンプルの分析)
2%、0.1%及び0.01%血清のためのカスタマイズ・ストックアプタマー溶液を1xSB17、0.05%ツイン-20で2x濃度で製造した。
零下80℃で保管された凍結100%の血清アリコートを5分間、25℃の水槽に入れた。解凍したサンプルを氷上に載置し、ゆっくりと渦流が起きるようにしておき、その後、再び氷上に載置した。
3つの加熱-冷却アプタマー溶液を体積55ulの適正なサンプル希釈液に移動させた。サンプルとアプタマー溶液をピペッティングして混合し、ホイールカバーを覆った。その後、前記プレートを3時間、37℃の培養器に置いた。
平衡結合段階の後、アプタマー-サンプル混合液100ulをストレプトアビジンでコーティングされた新しいプレートに移し、該プレートをサーモミキサ(thermomixer)に置いて、30分間(800rpmで)混合しながら37℃で培養した。光を避けるために、前記プレートをキャッチ1段階の間、覆っておいた。
キャッチ1段階の後、前記プレートをEL406洗浄器とディスペンサに置いた。前記EL406洗浄器とディスペンサは、次の段階を実施するようにプログラム化されている:吸収されない物質は吸引によって除去し、ウェルは1mMのデキストラン硫酸と500uMのビオチンを補充した300ulの緩衝液PB1で4回洗浄した。その後、ウェルを300ulの緩衝液PB1で更に3回洗浄した。
プレートをEL406洗浄器とディスペンサから取り出して20分間5cm離れた紫外線光源(LED紫外線光源)の下に配置されたサーモミキサに載置した。前記サーモミキサは、800rpm及びRTにセッティングされた。5分間照射した後、サンプルを洗浄した新たなストレプトアビジン・コーティングプレートに手作業で移した。キャッチ2段階は10分間、800rpm及び常温のサーモミキサで行われた。
キャッチ2段階の後、前記プレートをEL406洗浄器とディスペンサに載置した。前記EL406洗浄器とディスペンサは、次の段階を実施するようにプログラムされている:液体を吸引し、25%のプロフィレン・グリコールを補充した300ulの緩衝液PB1で8回洗浄した。ウェルを300ulの緩衝液PB1で5回洗浄し、最終洗浄液を吸引した。100ulのCAPSO溶出緩衝液を添加し、アプタマーを5分間振りながら溶出した。
これらの自動化段階の後、前記のプレートをプレート洗浄器のデッキから取り出し、90ulのサンプルアリコートを手作業で10uLの中性化緩衝液を含んでいるPCRプレートのウェルに移した。
微小球体(microsphere)を浮遊させるために、60秒間微小球体のストック溶液に渦流を起こして超音波処理を施した。浮遊する微小球体は、1.5xTMAC混成化溶液で毎反応当たり2000個の微小球体に希釈され、渦流及び超音波処理を施して混合された。毎反応当たり33uLのビード混合液を96-ウェルPCRプレートに移した。1xTE緩衝液で15nMビオチン化された検出オリゴヌクレオチド・ストック7ulを毎反応ごとに添加して混合した。中性化された検定サンプル10ulを添加し、前記プレートをシリコンキャップマットシールで封じた。前記プレートをまず5分間96Cで培養し、遺伝子増幅器で一晩の間に攪拌せずに50Cで培養した。フィルタープレートを0.5%BSAが補充された0.005xTMAC混成化溶液で予め浸しておいた。前記の混成化反応によりサンプル全体をフィルタープレートに移した。前記混成化プレートは0.5%BSAが補充された0.005xTMAC混成化溶液75ulで洗浄し、残存の物質はフィルタープレートに移した。サンプルを緩い真空下でフィルターリングした。前記フィルタープレートは、0.5%BSAが補充された0.005x TMAC混成化溶液75ulで1回洗浄し、フィルタープレートにある微小球体はサンプル緩衝液で更に1回浮遊処理を施した。フィルタープレートは遮光して1000rpmで5分間サーモミキサで培養した。その後、フィルタープレートを0.5%BSAを含む0.005xTMAC溶液で洗浄した。0.5%BSAを含む0.005xTMAC溶液で10ug/ml SAPE 075ulを各反応ごとに添加し、1時間1000rpmで25℃のサーモミキサで培養した。フィルタープレートを0.5%BSAを含む0.005xTMAC溶液で2回洗浄し、フィルタープレートにある微小球体は0.5%BSAを含む0.005xTMAC混成化溶液75ulで更に1回浮遊処理を施し、XPonent3.0ソフトウェアを稼動するルミネックス200器具上で分析した。7500〜18000の高PMT調整及びダブレット判別器のセッティング下で、ビード類型当たりに少なくとも100個の微小球体を計数した。
(実施形態3:バイオマーカーの識別)
(実施形態4:非小細胞肺癌のための単純ベイズ分類器トレーニング)
事後確率(posterior)=尤度(likelihood)×事前確率(prior)/証拠(evidence)
P(d|x)/P(c|x)=p(d)/(1−p(d)×Pi(p(x|d)/p(x|c))
対数尤度比(P(d|x)/P(c|x))は、疾病の状態を区分するための単一スコアで用いられる。
(実施形態5)
(実施形態6:7-マーカー分類器の検証)
(実施形態7:従来の血液テストと性能比較、Cyfra 21−1)
Claims (28)
- 表2に記載のバイオマーカータンパク質のうちN個を含むバイオマーカーパネルを提供する段階と、
前記パネルのN個のバイオマーカータンパク質とそれぞれ対応するバイオマーカー値を付与するために、ヒトより得られた生物学的サンプルから前記バイオマーカータンパク質を検出する段階とを含み、
前記Nは少なくとも2である整数であり、
前記肺癌は、前記バイオマーカー値に基づいて診断されることを特徴とするヒトの肺癌を診断するための方法。 - 前記バイオマーカー値を検出する段階は、生体内検定を行う段階を含むことを特徴とする、請求項1に記載の方法。
- 前記生体内検定は、前記バイオマーカータンパク質それぞれに対応する1つの捕捉試薬を含み、アプタマー、抗体及び核酸プローブからなる群より少なくとも1つの捕捉試薬を選択する段階を更に含むことを特徴とする、請求項2に記載の方法。
- 前記少なくとも1つの捕捉試薬は、アプタマーであることを特徴とする、請求項3に記載の方法。
- 前記生物学的サンプルは、全血、血漿及び血清からなる群より選択されることを特徴とする、請求項1に記載の方法。
- 前記生物学的サンプルは血清であることを特徴とする、請求項1に記載の方法。
- 前記ヒトはアジア人であることを特徴とする、請求項1に記載の方法。
- 前記ヒトは喫煙者であることを特徴とする、請求項1に記載の方法。
- 前記ヒトは悪性肺結節を持つことを特徴とする、請求項1に記載の方法。
- 前記Nは、少なくとも3であることを特徴とする、請求項1に記載の方法。
- 前記Nは少なくとも4であることを特徴とする、請求項1に記載の方法。
- 前記Nは少なくとも5であることを特徴とする、請求項1に記載の方法。
- 前記Nは少なくとも6であることを特徴とする、請求項1に記載の方法。
- 前記Nは少なくとも7であることを特徴とする、請求項1に記載の方法。
- 前記バイオマーカー値は、補体成分C9、炭酸脱水酵素(carbonic anhydrase)6(CA6)、C-反応性タンパク質(CRP)、表皮成長因子受容体1(EGFR1)、マトリックスメタロプロテアーゼ7(MMP7)、アルファ(α)1-アンチプロテアーゼ(SERPINA3)及び幹細胞成長因子受容体(KIT)の測定値を有することを特徴とする、請求項1に記載の方法。
- 前記バイオマーカー値は、リアルタイムPCR、マイクロアレイ及びルミネックスマイクロビーズ検定法(Luminex microbead assay)からなる群より測定されることを特徴とする、請求項1に記載の方法。
- 前記肺癌は統計的な方法で診断されることを特徴とする、請求項1に記載の方法。
- 前記統計的な方法は、線形判別分析、ロジスティック回帰分析、ナイーブベイズ分類、サポートベクターマシン及びランダムフォレスト(random forest)からなる群より選択されることを特徴とする、請求項1に記載の方法。
- ヒトの非小細胞肺癌を診断するためのタンパク質バイオマーカーパネルにおいて、前記パネルは、KITを含む表2に記載のバイオマーカータンパク質のうちN個のバイオマーカータンパク質を含み、Nは少なくとも2であることを特徴とするパネル。
- 前記Nは少なくとも3であることを特徴とする、請求項19に記載のパネル。
- 前記Nは少なくとも4であることを特徴とする、請求項19に記載のパネル。
- 前記Nは少なくとも5であることを特徴とする、請求項19に記載のパネル。
- 前記Nは少なくとも6であることを特徴とする、請求項19に記載のパネル。
- 前記Nは少なくとも7であることを特徴とする、請求項19に記載のパネル。
- 前記パネルは、補体成分C9、炭酸脱水酵素(carbonic anhydrase)6(CA6)、C-反応性タンパク質(CRP)、表皮成長因子受容体1(EGFR1)、マトリックスメタロプロテアーゼ7(MMP7)、アルファ(α)1-アンチプロテアーゼ(SERPINA3)及び幹細胞成長因子受容体(KIT)の測定値を有することを特徴とする、請求項19に記載のパネル。
- 前記ヒトはアジア人であることを特徴とする、請求項19に記載のパネル。
- 前記ヒトは喫煙者であることを特徴とする、請求項19に記載のパネル。
- 前記ヒトは悪性肺結節を持つことを特徴とする、請求項19に記載のパネル。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/KR2015/009552 WO2017043679A1 (en) | 2015-09-11 | 2015-09-11 | Protein biomarker panel for detecting non-small cell lung cancer and method for diagnosing a non-small cell lung cancer by the use thereof |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018528441A true JP2018528441A (ja) | 2018-09-27 |
JP2018528441A5 JP2018528441A5 (ja) | 2021-03-25 |
JP6857185B2 JP6857185B2 (ja) | 2021-04-14 |
Family
ID=58239995
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018533586A Active JP6857185B2 (ja) | 2015-09-11 | 2015-09-11 | 非小細胞肺癌診断用タンパク質バイオマーカーパネル及びこれを用いた非小細胞肺癌診断方法 |
Country Status (4)
Country | Link |
---|---|
JP (1) | JP6857185B2 (ja) |
KR (2) | KR102078310B1 (ja) |
CN (1) | CN108026584B (ja) |
WO (1) | WO2017043679A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3884259A1 (en) * | 2018-11-20 | 2021-09-29 | Ventana Medical Systems, Inc. | Methods and systems for preparing and analyzing cellular samples for morphological characteristics and biomarker expression |
TWI758670B (zh) * | 2018-12-24 | 2022-03-21 | 奎克生技光電股份有限公司 | 健康風險評估方法 |
CN110333341A (zh) * | 2019-07-04 | 2019-10-15 | 浙江理工大学 | 一种基于蛋白质芯片技术鉴别丝织品文物样的方法 |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002053592A1 (fr) * | 2000-12-28 | 2002-07-11 | Shionogi & Co., Ltd. | Nouveau polypeptide et son adn |
US20090068685A1 (en) * | 2007-09-11 | 2009-03-12 | Cancer Prevention And Cure, Ltd. | Method of Identifying Biomarkers in Human Serum Indicative of Pathologies of Human Lung Tissues |
WO2010030697A1 (en) * | 2008-09-09 | 2010-03-18 | Somalogic, Inc. | Lung cancer biomarkers and uses thereof |
WO2011015602A2 (en) * | 2009-08-04 | 2011-02-10 | Biosystems International Sas | Lung cancer biomarkers |
WO2011109440A1 (en) * | 2010-03-01 | 2011-09-09 | Caris Life Sciences Luxembourg Holdings | Biomarkers for theranostics |
WO2012006632A2 (en) * | 2010-07-09 | 2012-01-12 | Somalogic, Inc. | Lung cancer biomarkers and uses thereof |
US20120190050A1 (en) * | 2009-07-23 | 2012-07-26 | National University Of Singapore | Cancer biomarker and the use thereof |
JP2012520469A (ja) * | 2009-03-12 | 2012-09-06 | キャンサー・プリヴェンション・アンド・キュア,リミテッド | 性別に基づく疾病の識別・評価・予防及び治療を含む、肺病の識別・評価・予防及び治療の方法並びにそのキット |
WO2013152989A2 (en) * | 2012-04-10 | 2013-10-17 | Eth Zurich | Biomarker assay and uses thereof for diagnosis, therapy selection, and prognosis of cancer |
JP2015501154A (ja) * | 2011-10-24 | 2015-01-15 | ソマロジック・インコーポレーテッド | 肺癌バイオマーカーおよびその使用 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101970908B1 (ko) * | 2008-02-01 | 2019-04-19 | 더 제너럴 하스피탈 코포레이션 | 의학적 질환 및 병태의 진단, 예후, 및 치료에 있어서 미세소포체의 용도 |
WO2013022995A2 (en) * | 2011-08-08 | 2013-02-14 | Caris Life Sciences Luxembourg Holdings, S.A.R.L. | Biomarker compositions and methods |
JP2014519340A (ja) * | 2011-06-16 | 2014-08-14 | カリス ライフ サイエンシズ ルクセンブルク ホールディングス エス.アー.エール.エル. | バイオマーカー組成物および方法 |
WO2013033019A1 (en) * | 2011-08-31 | 2013-03-07 | University Of Utah Research Foundation | Methods for determining the integrity of a biological sample |
CN103702835B (zh) | 2011-10-24 | 2016-04-06 | 惠普发展公司,有限责任合伙企业 | 流体喷出装置及其方法 |
-
2015
- 2015-09-11 JP JP2018533586A patent/JP6857185B2/ja active Active
- 2015-09-11 CN CN201580083066.4A patent/CN108026584B/zh active Active
- 2015-09-11 WO PCT/KR2015/009552 patent/WO2017043679A1/en active Application Filing
- 2015-09-11 KR KR1020187007151A patent/KR102078310B1/ko active IP Right Grant
- 2015-09-11 KR KR1020207004010A patent/KR102087373B1/ko active IP Right Grant
Patent Citations (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002053592A1 (fr) * | 2000-12-28 | 2002-07-11 | Shionogi & Co., Ltd. | Nouveau polypeptide et son adn |
US20090068685A1 (en) * | 2007-09-11 | 2009-03-12 | Cancer Prevention And Cure, Ltd. | Method of Identifying Biomarkers in Human Serum Indicative of Pathologies of Human Lung Tissues |
JP2012502281A (ja) * | 2008-09-09 | 2012-01-26 | ソマロジック・インコーポレーテッド | 肺癌バイオマーカーとその使用 |
WO2010030697A1 (en) * | 2008-09-09 | 2010-03-18 | Somalogic, Inc. | Lung cancer biomarkers and uses thereof |
JP2012520469A (ja) * | 2009-03-12 | 2012-09-06 | キャンサー・プリヴェンション・アンド・キュア,リミテッド | 性別に基づく疾病の識別・評価・予防及び治療を含む、肺病の識別・評価・予防及び治療の方法並びにそのキット |
US20120190050A1 (en) * | 2009-07-23 | 2012-07-26 | National University Of Singapore | Cancer biomarker and the use thereof |
WO2011015602A2 (en) * | 2009-08-04 | 2011-02-10 | Biosystems International Sas | Lung cancer biomarkers |
WO2011109440A1 (en) * | 2010-03-01 | 2011-09-09 | Caris Life Sciences Luxembourg Holdings | Biomarkers for theranostics |
JP2013521502A (ja) * | 2010-03-01 | 2013-06-10 | カリス ライフ サイエンシズ ルクセンブルク ホールディングス | セラノーシスのためのバイオマーカー |
WO2012006632A2 (en) * | 2010-07-09 | 2012-01-12 | Somalogic, Inc. | Lung cancer biomarkers and uses thereof |
JP2013532295A (ja) * | 2010-07-09 | 2013-08-15 | ソマロジック・インコーポレーテッド | 肺癌バイオマーカーとその使用 |
JP2015501154A (ja) * | 2011-10-24 | 2015-01-15 | ソマロジック・インコーポレーテッド | 肺癌バイオマーカーおよびその使用 |
WO2013152989A2 (en) * | 2012-04-10 | 2013-10-17 | Eth Zurich | Biomarker assay and uses thereof for diagnosis, therapy selection, and prognosis of cancer |
Non-Patent Citations (2)
Title |
---|
MEHAN, M.R. ET AL.: "Validation of a blood protein signature for non-small cell lung cancer", CLINICAL PROTEOMICS, vol. 11, no. 21, JPN6019039412, 1 August 2014 (2014-08-01), pages 1 - 12, ISSN: 0004132500 * |
NADAL, E. ET AL.: "A Novel Serum 4-microRNA Signature for Lung Cancer Detection", SCIENTIFIC REPORTS, vol. Vol. 5, 12464, JPN6019008422, 2015, pages 1 - 9, ISSN: 0004132501 * |
Also Published As
Publication number | Publication date |
---|---|
CN108026584A (zh) | 2018-05-11 |
JP6857185B2 (ja) | 2021-04-14 |
KR20200020958A (ko) | 2020-02-26 |
CN108026584B (zh) | 2021-12-10 |
KR102078310B1 (ko) | 2020-02-19 |
KR20180036787A (ko) | 2018-04-09 |
KR102087373B1 (ko) | 2020-03-10 |
WO2017043679A1 (en) | 2017-03-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR101658347B1 (ko) | 폐암 바이오마커 및 그것들의 용도 | |
KR101921945B1 (ko) | 폐암 바이오마커 및 그것의 용도 | |
KR101857462B1 (ko) | 췌장암 바이오마커 및 그것의 용도 | |
KR101870123B1 (ko) | 폐암 바이오마커 및 그것의 용도 | |
US20120143805A1 (en) | Cancer Biomarkers and Uses Thereof | |
WO2011031344A1 (en) | Cancer biomarkers and uses thereof | |
JP6857185B2 (ja) | 非小細胞肺癌診断用タンパク質バイオマーカーパネル及びこれを用いた非小細胞肺癌診断方法 | |
US20220065872A1 (en) | Lung Cancer Biomarkers and Uses Thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180405 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190227 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190312 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190516 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191015 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200110 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200311 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200818 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201112 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20201208 |
|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20210215 |
|
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: 20210309 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210319 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6857185 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |