ES2772701T3 - Uso de nucleosomas libres de células como biomarcadores en muestras de esputo - Google Patents
Uso de nucleosomas libres de células como biomarcadores en muestras de esputo Download PDFInfo
- Publication number
- ES2772701T3 ES2772701T3 ES16736594T ES16736594T ES2772701T3 ES 2772701 T3 ES2772701 T3 ES 2772701T3 ES 16736594 T ES16736594 T ES 16736594T ES 16736594 T ES16736594 T ES 16736594T ES 2772701 T3 ES2772701 T3 ES 2772701T3
- Authority
- ES
- Spain
- Prior art keywords
- cell
- epigenetic
- free
- nucleosome
- nucleosomes
- 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
- 108010047956 Nucleosomes Proteins 0.000 title claims abstract description 226
- 210000001623 nucleosome Anatomy 0.000 title claims abstract description 225
- 206010036790 Productive cough Diseases 0.000 title claims abstract description 135
- 208000024794 sputum Diseases 0.000 title claims abstract description 135
- 210000003802 sputum Anatomy 0.000 title claims abstract description 135
- 239000000090 biomarker Substances 0.000 title claims abstract description 102
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 77
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 73
- 201000005202 lung cancer Diseases 0.000 claims abstract description 73
- 238000001514 detection method Methods 0.000 claims abstract description 48
- 238000003745 diagnosis Methods 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 127
- 230000001973 epigenetic effect Effects 0.000 claims description 118
- 108010033040 Histones Proteins 0.000 claims description 96
- 210000004027 cell Anatomy 0.000 claims description 60
- 239000011230 binding agent Substances 0.000 claims description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 51
- 230000004048 modification Effects 0.000 claims description 46
- 238000012986 modification Methods 0.000 claims description 46
- 201000010099 disease Diseases 0.000 claims description 42
- 238000003018 immunoassay Methods 0.000 claims description 37
- 108090000623 proteins and genes Proteins 0.000 claims description 35
- 241001465754 Metazoa Species 0.000 claims description 24
- 238000012544 monitoring process Methods 0.000 claims description 22
- 238000002560 therapeutic procedure Methods 0.000 claims description 22
- 230000008836 DNA modification Effects 0.000 claims description 21
- 108010029485 Protein Isoforms Proteins 0.000 claims description 19
- 102000001708 Protein Isoforms Human genes 0.000 claims description 19
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 17
- 102000004169 proteins and genes Human genes 0.000 claims description 17
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 17
- 238000005259 measurement Methods 0.000 claims description 12
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 11
- 230000001413 cellular effect Effects 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 9
- 238000004393 prognosis Methods 0.000 claims description 9
- 238000002487 chromatin immunoprecipitation Methods 0.000 claims description 8
- 230000001323 posttranslational effect Effects 0.000 claims description 7
- 230000003902 lesion Effects 0.000 claims description 6
- 210000005265 lung cell Anatomy 0.000 claims description 4
- 102100023919 Histone H2A.Z Human genes 0.000 claims description 3
- 101000905054 Homo sapiens Histone H2A.Z Proteins 0.000 claims description 3
- BDJRBEYXGGNYIS-UHFFFAOYSA-N Nonanedioid acid Natural products OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 claims description 3
- 230000000984 immunochemical effect Effects 0.000 claims description 2
- 238000004949 mass spectrometry Methods 0.000 claims description 2
- 239000000523 sample Substances 0.000 description 75
- 206010028980 Neoplasm Diseases 0.000 description 70
- 238000012360 testing method Methods 0.000 description 54
- 201000011510 cancer Diseases 0.000 description 49
- 210000003483 chromatin Anatomy 0.000 description 38
- 108010077544 Chromatin Proteins 0.000 description 37
- 239000012634 fragment Substances 0.000 description 34
- 108020004414 DNA Proteins 0.000 description 27
- 239000003814 drug Substances 0.000 description 24
- 238000011282 treatment Methods 0.000 description 22
- 229940079593 drug Drugs 0.000 description 20
- 238000003556 assay Methods 0.000 description 19
- 239000003446 ligand Substances 0.000 description 19
- 125000003729 nucleotide group Chemical group 0.000 description 15
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 14
- 238000002965 ELISA Methods 0.000 description 13
- 102000006947 Histones Human genes 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 230000035772 mutation Effects 0.000 description 12
- 238000011002 quantification Methods 0.000 description 11
- 238000012216 screening Methods 0.000 description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 239000012472 biological sample Substances 0.000 description 9
- 230000011987 methylation Effects 0.000 description 9
- 238000007069 methylation reaction Methods 0.000 description 9
- 230000035945 sensitivity Effects 0.000 description 9
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 210000004072 lung Anatomy 0.000 description 8
- 230000003211 malignant effect Effects 0.000 description 8
- 102100039869 Histone H2B type F-S Human genes 0.000 description 7
- 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 description 7
- 230000002583 anti-histone Effects 0.000 description 7
- 230000004481 post-translational protein modification Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000007067 DNA methylation Effects 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000002405 diagnostic procedure Methods 0.000 description 6
- 150000007523 nucleic acids Chemical group 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 208000003200 Adenoma Diseases 0.000 description 5
- 206010001233 Adenoma benign Diseases 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108091023037 Aptamer Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 229940122825 Histone methyltransferase inhibitor Drugs 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 239000012491 analyte Substances 0.000 description 4
- 230000003172 anti-dna Effects 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000002651 drug therapy Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 239000006199 nebulizer Substances 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 3
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000002591 computed tomography Methods 0.000 description 3
- 229940104302 cytosine Drugs 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000009509 drug development Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000000672 surface-enhanced laser desorption--ionisation Methods 0.000 description 3
- 238000001356 surgical procedure Methods 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
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 102000012406 Carcinoembryonic Antigen Human genes 0.000 description 2
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- 230000030933 DNA methylation on cytosine Effects 0.000 description 2
- 108010022894 Euchromatin Proteins 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 108010034791 Heterochromatin Proteins 0.000 description 2
- 102100034533 Histone H2AX Human genes 0.000 description 2
- 101710195387 Histone H3.2 Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001067891 Homo sapiens Histone H2AX Proteins 0.000 description 2
- 108050002584 Septin 9 Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000012575 bio-layer interferometry Methods 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000012350 deep sequencing Methods 0.000 description 2
- 238000003748 differential diagnosis Methods 0.000 description 2
- 239000012470 diluted sample Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000007877 drug screening Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 230000004076 epigenetic alteration Effects 0.000 description 2
- 230000006718 epigenetic regulation Effects 0.000 description 2
- 210000000632 euchromatin Anatomy 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000004458 heterochromatin Anatomy 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000013198 immunometric assay Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 238000003819 low-pressure liquid chromatography Methods 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000013178 mathematical model Methods 0.000 description 2
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- -1 or His tag (eg Chemical compound 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 238000010798 ubiquitination Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- XSYUPRQVAHJETO-WPMUBMLPSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-imidaz Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 XSYUPRQVAHJETO-WPMUBMLPSA-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
- 239000004475 Arginine Substances 0.000 description 1
- 208000034048 Asymptomatic disease Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102100031680 Beta-catenin-interacting protein 1 Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 206010061386 Chest injury Diseases 0.000 description 1
- 102100034528 Core histone macro-H2A.1 Human genes 0.000 description 1
- 101710184999 Core histone macro-H2A.1 Proteins 0.000 description 1
- 102100030670 Core histone macro-H2A.2 Human genes 0.000 description 1
- 101710185000 Core histone macro-H2A.2 Proteins 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108010009540 DNA (Cytosine-5-)-Methyltransferase 1 Proteins 0.000 description 1
- 102100036279 DNA (cytosine-5)-methyltransferase 1 Human genes 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000006429 DNA hypomethylation Effects 0.000 description 1
- 229940126190 DNA methyltransferase inhibitor Drugs 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 102100024739 E3 ubiquitin-protein ligase UHRF1 Human genes 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 102000000849 HMGB Proteins Human genes 0.000 description 1
- 108010001860 HMGB Proteins Proteins 0.000 description 1
- 102000018802 High Mobility Group Proteins Human genes 0.000 description 1
- 101710176246 High mobility group protein Proteins 0.000 description 1
- 102100022130 High mobility group protein B3 Human genes 0.000 description 1
- 101710195517 Histone H2AX Proteins 0.000 description 1
- 102100034535 Histone H3.1 Human genes 0.000 description 1
- 101710195388 Histone H3.1 Proteins 0.000 description 1
- 102100034536 Histone H3.1t Human genes 0.000 description 1
- 102100033636 Histone H3.2 Human genes 0.000 description 1
- 101710195400 Histone H3.3 Proteins 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 description 1
- 101000993469 Homo sapiens Beta-catenin-interacting protein 1 Proteins 0.000 description 1
- 101000760417 Homo sapiens E3 ubiquitin-protein ligase UHRF1 Proteins 0.000 description 1
- 101001006375 Homo sapiens High mobility group nucleosome-binding domain-containing protein 4 Proteins 0.000 description 1
- 101001045794 Homo sapiens High mobility group protein B3 Proteins 0.000 description 1
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108091092878 Microsatellite Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 102000009339 Proliferating Cell Nuclear Antigen Human genes 0.000 description 1
- 206010056342 Pulmonary mass Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 102000012060 Septin 9 Human genes 0.000 description 1
- 101001081186 Tetrahymena pyriformis High mobility group protein Proteins 0.000 description 1
- 101000898914 Tetrahymena thermophila (strain SB210) Histone H2A.1 Proteins 0.000 description 1
- 208000029224 Thoracic injury Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 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
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- OHDRQQURAXLVGJ-AXMZSLBLSA-N azane;(2z)-3-ethyl-2-[(z)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N\N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-AXMZSLBLSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 230000033228 biological regulation Effects 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
- 239000000872 buffer Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 125000001369 canonical nucleoside group Chemical group 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 238000011976 chest X-ray Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000002967 competitive immunoassay Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000104 diagnostic biomarker Substances 0.000 description 1
- 230000009274 differential gene expression Effects 0.000 description 1
- 239000003968 dna methyltransferase inhibitor Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000004034 genetic regulation Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 238000007031 hydroxymethylation reaction Methods 0.000 description 1
- 230000006607 hypermethylation Effects 0.000 description 1
- 238000003317 immunochromatography Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 201000004933 in situ carcinoma Diseases 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000007479 molecular analysis Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 238000011338 personalized therapy Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 230000002974 pharmacogenomic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000092 prognostic biomarker Substances 0.000 description 1
- 238000002331 protein detection Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 201000003957 thoracic cancer Diseases 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000001262 western blot Methods 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6875—Nucleoproteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/12—Pulmonary diseases
- G01N2800/122—Chronic or obstructive airway disorders, e.g. asthma COPD
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Transplantation (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1511512.4A GB201511512D0 (en) | 2015-07-01 | 2015-07-01 | Use of cell-free nucleosomes as biomarkers |
| PCT/GB2016/051994 WO2017001863A1 (en) | 2015-07-01 | 2016-07-01 | Use of cell-free nucleosomes as biomarkers in sputum samples |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2772701T3 true ES2772701T3 (es) | 2020-07-08 |
Family
ID=53872486
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16736594T Active ES2772701T3 (es) | 2015-07-01 | 2016-07-01 | Uso de nucleosomas libres de células como biomarcadores en muestras de esputo |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20180306804A1 (enExample) |
| EP (1) | EP3317671B1 (enExample) |
| JP (1) | JP7094700B2 (enExample) |
| CN (1) | CN108450000A (enExample) |
| ES (1) | ES2772701T3 (enExample) |
| GB (1) | GB201511512D0 (enExample) |
| WO (1) | WO2017001863A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2019228625B2 (en) * | 2018-03-01 | 2024-11-07 | Epicypher, Inc. | Quantification of nucleosome modifications using chemically-defined recombinant nucleosomes |
| US11154240B2 (en) | 2019-04-02 | 2021-10-26 | Kpn Innovations Llc | Methods and systems for utilizing diagnostics for informed vibrant constitutional guidance |
| GB201906199D0 (en) * | 2019-05-02 | 2019-06-19 | Belgian Volition Sprl | Method for the detection of cancer |
| BR112022010774A2 (pt) * | 2019-12-02 | 2022-08-23 | Belgian Volition Srl | Uso de nucleossomos livres de células como biomarcadores |
| US11289206B2 (en) | 2020-06-02 | 2022-03-29 | Kpn Innovations, Llc. | Artificial intelligence methods and systems for constitutional analysis using objective functions |
| US12176108B2 (en) | 2020-06-02 | 2024-12-24 | Kpn Innovations Llc | Artificial intelligence methods and systems for constitutional analysis using objective functions |
| US11211158B1 (en) | 2020-08-31 | 2021-12-28 | Kpn Innovations, Llc. | System and method for representing an arranged list of provider aliment possibilities |
| GB202310137D0 (en) * | 2023-07-03 | 2023-08-16 | Belgian Volition Srl | Method for the detection of cancer |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7229772B1 (en) * | 1998-03-18 | 2007-06-12 | Roche Diagnostics Gmbh | Detection of apoptotic products |
| GB201012662D0 (en) * | 2010-07-28 | 2010-09-15 | Valirx Plc | Method for detecting the presence of a gynaecological growth |
| GB201115098D0 (en) * | 2011-09-01 | 2011-10-19 | Belgian Volition Sa | Method for detecting nucleosomes containing histone variants |
| GB201115095D0 (en) * | 2011-09-01 | 2011-10-19 | Singapore Volition Pte Ltd | Method for detecting nucleosomes containing nucleotides |
| SG10201604081YA (en) * | 2011-12-07 | 2016-07-28 | Singapore Volition Pte Ltd | Method for detecting nucleosome adducts |
| GB201303575D0 (en) * | 2013-02-28 | 2013-04-10 | Singapore Volition Pte Ltd | Method for detecting histone modifications in nucleosomes |
| WO2015048535A1 (en) * | 2013-09-27 | 2015-04-02 | Natera, Inc. | Prenatal diagnostic resting standards |
-
2015
- 2015-07-01 GB GBGB1511512.4A patent/GB201511512D0/en not_active Ceased
-
2016
- 2016-07-01 JP JP2017568274A patent/JP7094700B2/ja active Active
- 2016-07-01 WO PCT/GB2016/051994 patent/WO2017001863A1/en not_active Ceased
- 2016-07-01 ES ES16736594T patent/ES2772701T3/es active Active
- 2016-07-01 CN CN201680050736.7A patent/CN108450000A/zh active Pending
- 2016-07-01 EP EP16736594.9A patent/EP3317671B1/en active Active
- 2016-07-01 US US15/738,082 patent/US20180306804A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP7094700B2 (ja) | 2022-07-04 |
| EP3317671A1 (en) | 2018-05-09 |
| US20180306804A1 (en) | 2018-10-25 |
| GB201511512D0 (en) | 2015-08-12 |
| HK1255151A1 (en) | 2019-08-09 |
| CN108450000A (zh) | 2018-08-24 |
| JP2018529931A (ja) | 2018-10-11 |
| EP3317671B1 (en) | 2019-11-13 |
| WO2017001863A1 (en) | 2017-01-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2772701T3 (es) | Uso de nucleosomas libres de células como biomarcadores en muestras de esputo | |
| ES2955475T3 (es) | Método para detectar nucleosomas que contienen variantes de histonas | |
| ES2663603T3 (es) | Procedimiento para detectar nucleosomas | |
| ES2717659T3 (es) | Procedimiento para la detección de nucleosomas que contienen nucleótidos | |
| ES2649404T3 (es) | Procedimiento para detectar aductos de nucleosomas | |
| US20170003296A1 (en) | Method for detecting histone modifications in nucleosomes | |
| ES2861440T5 (en) | Use of nucleosome-transcription factor complexes for cancer detection | |
| US20160003848A1 (en) | Method for predicting therapy efficacy using nucleosome structure biomarkers | |
| ES2775178T3 (es) | Uso de nucleosomas libres de células como biomarcadores en muestras fecales | |
| JP2024504105A (ja) | 肺癌の検出のための方法 | |
| CN114286942B (zh) | 检测癌症的方法 | |
| HK1255151B (en) | Use of cell-free nucleosomes as biomarkers in sputum samples | |
| HK1255090A1 (en) | Use of cell-free nucleosomes as biomarkers in fecal samples | |
| HK1255090B (en) | Use of cell-free nucleosomes as biomarkers in fecal samples |