DK2198042T3 - New markers for bladder cancer detection - Google Patents
New markers for bladder cancer detection Download PDFInfo
- Publication number
- DK2198042T3 DK2198042T3 DK08802026.8T DK08802026T DK2198042T3 DK 2198042 T3 DK2198042 T3 DK 2198042T3 DK 08802026 T DK08802026 T DK 08802026T DK 2198042 T3 DK2198042 T3 DK 2198042T3
- Authority
- DK
- Denmark
- Prior art keywords
- nid2
- methylation
- sample
- detecting
- gene
- Prior art date
Links
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 title claims description 108
- 206010005003 Bladder cancer Diseases 0.000 title claims description 106
- 201000005112 urinary bladder cancer Diseases 0.000 title claims description 101
- 238000001514 detection method Methods 0.000 title claims description 58
- 108090000623 proteins and genes Proteins 0.000 claims description 202
- 238000000034 method Methods 0.000 claims description 179
- 239000000523 sample Substances 0.000 claims description 142
- 210000002700 urine Anatomy 0.000 claims description 129
- 230000011987 methylation Effects 0.000 claims description 103
- 238000007069 methylation reaction Methods 0.000 claims description 103
- 101000601048 Homo sapiens Nidogen-2 Proteins 0.000 claims description 102
- 102100037371 Nidogen-2 Human genes 0.000 claims description 100
- 108010079362 Core Binding Factor Alpha 3 Subunit Proteins 0.000 claims description 91
- 102000012666 Core Binding Factor Alpha 3 Subunit Human genes 0.000 claims description 90
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 claims description 76
- 101000899361 Homo sapiens Bone morphogenetic protein 7 Proteins 0.000 claims description 76
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 claims description 70
- 102100025176 Cyclin-A1 Human genes 0.000 claims description 70
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 claims description 70
- 101000934314 Homo sapiens Cyclin-A1 Proteins 0.000 claims description 70
- 101000785523 Homo sapiens Tight junction protein ZO-2 Proteins 0.000 claims description 66
- 101000679903 Homo sapiens Tumor necrosis factor receptor superfamily member 25 Proteins 0.000 claims description 66
- 102100026637 Tight junction protein ZO-2 Human genes 0.000 claims description 66
- 102100033281 ADP-ribosylation factor GTPase-activating protein 3 Human genes 0.000 claims description 65
- 101000927505 Homo sapiens ADP-ribosylation factor GTPase-activating protein 3 Proteins 0.000 claims description 65
- 101000988395 Homo sapiens PDZ and LIM domain protein 4 Proteins 0.000 claims description 65
- 102100029178 PDZ and LIM domain protein 4 Human genes 0.000 claims description 65
- 102100022203 Tumor necrosis factor receptor superfamily member 25 Human genes 0.000 claims description 65
- 101000713585 Homo sapiens Tubulin beta-4A chain Proteins 0.000 claims description 64
- 102100036788 Tubulin beta-4A chain Human genes 0.000 claims description 64
- 102100035080 BDNF/NT-3 growth factors receptor Human genes 0.000 claims description 62
- 101000596896 Homo sapiens BDNF/NT-3 growth factors receptor Proteins 0.000 claims description 62
- 108010083162 Twist-Related Protein 1 Proteins 0.000 claims description 62
- 101001043321 Homo sapiens Lysyl oxidase homolog 1 Proteins 0.000 claims description 61
- 101000586302 Homo sapiens Oncostatin-M-specific receptor subunit beta Proteins 0.000 claims description 61
- 102100021958 Lysyl oxidase homolog 1 Human genes 0.000 claims description 61
- 102100030098 Oncostatin-M-specific receptor subunit beta Human genes 0.000 claims description 60
- 230000003321 amplification Effects 0.000 claims description 54
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 54
- 238000007855 methylation-specific PCR Methods 0.000 claims description 47
- ONCZDRURRATYFI-QTCHDTBASA-N methyl (2z)-2-methoxyimino-2-[2-[[(e)-1-[3-(trifluoromethyl)phenyl]ethylideneamino]oxymethyl]phenyl]acetate Chemical compound CO\N=C(/C(=O)OC)C1=CC=CC=C1CO\N=C(/C)C1=CC=CC(C(F)(F)F)=C1 ONCZDRURRATYFI-QTCHDTBASA-N 0.000 claims description 46
- 230000008995 epigenetic change Effects 0.000 claims description 44
- 230000035772 mutation Effects 0.000 claims description 37
- 238000004458 analytical method Methods 0.000 claims description 25
- 239000000872 buffer Substances 0.000 claims description 24
- 238000005119 centrifugation Methods 0.000 claims description 15
- -1 RASSF1A Proteins 0.000 claims description 12
- 125000003729 nucleotide group Chemical group 0.000 claims description 12
- 239000002773 nucleotide Substances 0.000 claims description 10
- 210000005068 bladder tissue Anatomy 0.000 claims description 8
- 230000000087 stabilizing effect Effects 0.000 claims description 8
- 101150025764 FGFR3 gene Proteins 0.000 claims description 5
- 230000006641 stabilisation Effects 0.000 claims description 3
- 238000011105 stabilization Methods 0.000 claims description 2
- 102000006280 Twist-Related Protein 1 Human genes 0.000 claims 6
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 description 90
- 239000013615 primer Substances 0.000 description 84
- 201000011510 cancer Diseases 0.000 description 72
- 102000053602 DNA Human genes 0.000 description 70
- 108020004414 DNA Proteins 0.000 description 70
- 102100030398 Twist-related protein 1 Human genes 0.000 description 55
- 238000003556 assay Methods 0.000 description 51
- 238000012360 testing method Methods 0.000 description 50
- 238000011282 treatment Methods 0.000 description 48
- 230000014509 gene expression Effects 0.000 description 35
- 230000035945 sensitivity Effects 0.000 description 33
- 150000007523 nucleic acids Chemical class 0.000 description 31
- 239000003550 marker Substances 0.000 description 30
- 210000001519 tissue Anatomy 0.000 description 30
- 102000039446 nucleic acids Human genes 0.000 description 29
- 108020004707 nucleic acids Proteins 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- 238000012549 training Methods 0.000 description 29
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 28
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 28
- 230000001973 epigenetic effect Effects 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 23
- 230000030279 gene silencing Effects 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 19
- 239000003153 chemical reaction reagent Substances 0.000 description 18
- 201000010099 disease Diseases 0.000 description 18
- 230000007067 DNA methylation Effects 0.000 description 16
- 206010044412 transitional cell carcinoma Diseases 0.000 description 16
- 230000000295 complement effect Effects 0.000 description 13
- 206010041823 squamous cell carcinoma Diseases 0.000 description 13
- 230000003019 stabilising effect Effects 0.000 description 13
- 239000012650 DNA demethylating agent Substances 0.000 description 12
- 229940045805 DNA demethylating agent Drugs 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 12
- 239000003968 dna methyltransferase inhibitor Substances 0.000 description 12
- 238000012545 processing Methods 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 108091029523 CpG island Proteins 0.000 description 10
- 229940126190 DNA methyltransferase inhibitor Drugs 0.000 description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 description 10
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 10
- 238000013459 approach Methods 0.000 description 10
- 238000003753 real-time PCR Methods 0.000 description 10
- 241000239226 Scorpiones Species 0.000 description 9
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 9
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 9
- 238000011160 research Methods 0.000 description 9
- 230000002485 urinary effect Effects 0.000 description 9
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 8
- 108091034117 Oligonucleotide Proteins 0.000 description 8
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 8
- 238000010240 RT-PCR analysis Methods 0.000 description 8
- 239000000975 dye Substances 0.000 description 8
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 8
- 230000002068 genetic effect Effects 0.000 description 8
- 238000012544 monitoring process Methods 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 238000011002 quantification Methods 0.000 description 8
- 239000013049 sediment Substances 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- 210000003443 bladder cell Anatomy 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 238000012163 sequencing technique Methods 0.000 description 7
- 238000002574 cystoscopy Methods 0.000 description 6
- 238000003066 decision tree Methods 0.000 description 6
- 230000004049 epigenetic modification Effects 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- 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 5
- 230000004075 alteration Effects 0.000 description 5
- 210000000349 chromosome Anatomy 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000002271 resection Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 208000016525 transitional cell neoplasm Diseases 0.000 description 5
- 229940035893 uracil Drugs 0.000 description 5
- 108091093088 Amplicon Proteins 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 4
- 101000712958 Homo sapiens Ras association domain-containing protein 1 Proteins 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 4
- 206010071019 Prostatic dysplasia Diseases 0.000 description 4
- 102100033243 Ras association domain-containing protein 1 Human genes 0.000 description 4
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
- 206010065584 Urethral stenosis Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000001124 body fluid Anatomy 0.000 description 4
- 239000010839 body fluid Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000002751 oligonucleotide probe Substances 0.000 description 4
- 208000003154 papilloma Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 201000007094 prostatitis Diseases 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 230000000171 quenching effect Effects 0.000 description 4
- 238000011897 real-time detection Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 4
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 201000001988 urethral stricture Diseases 0.000 description 4
- WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 description 3
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 3
- 206010071445 Bladder outlet obstruction Diseases 0.000 description 3
- 108091029430 CpG site Proteins 0.000 description 3
- 238000007399 DNA isolation Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108700024394 Exon Proteins 0.000 description 3
- 206010071289 Lower urinary tract symptoms Diseases 0.000 description 3
- 208000003800 Urinary Bladder Neck Obstruction Diseases 0.000 description 3
- 239000012491 analyte Substances 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 238000001369 bisulfite sequencing Methods 0.000 description 3
- 201000001531 bladder carcinoma Diseases 0.000 description 3
- 239000012830 cancer therapeutic Substances 0.000 description 3
- 239000013068 control sample Substances 0.000 description 3
- 201000003146 cystitis Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000006607 hypermethylation Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000002987 primer (paints) Substances 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 3
- 210000001635 urinary tract Anatomy 0.000 description 3
- 238000012800 visualization Methods 0.000 description 3
- 206010069754 Acquired gene mutation Diseases 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 229930024421 Adenine Natural products 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 208000009458 Carcinoma in Situ Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004533 Endonucleases Human genes 0.000 description 2
- 108091060211 Expressed sequence tag Proteins 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 101000756632 Homo sapiens Actin, cytoplasmic 1 Proteins 0.000 description 2
- 101000945496 Homo sapiens Proliferation marker protein Ki-67 Proteins 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- 102000016397 Methyltransferase Human genes 0.000 description 2
- 102000047918 Myelin Basic Human genes 0.000 description 2
- 102100036961 Nuclear mitotic apparatus protein 1 Human genes 0.000 description 2
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 2
- 102100034836 Proliferation marker protein Ki-67 Human genes 0.000 description 2
- 102000055027 Protein Methyltransferases Human genes 0.000 description 2
- 108700040121 Protein Methyltransferases Proteins 0.000 description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 241000270295 Serpentes Species 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 239000013584 assay control Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 230000004076 epigenetic alteration Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 201000004933 in situ carcinoma Diseases 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000007834 ligase chain reaction Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000007477 logistic regression Methods 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 231100001160 nonlethal Toxicity 0.000 description 2
- 108010036112 nuclear matrix protein 22 Proteins 0.000 description 2
- 238000007899 nucleic acid hybridization Methods 0.000 description 2
- 239000002853 nucleic acid probe Substances 0.000 description 2
- 238000002515 oligonucleotide synthesis Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 230000037452 priming Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003196 serial analysis of gene expression Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000037439 somatic mutation Effects 0.000 description 2
- 238000011895 specific detection Methods 0.000 description 2
- 208000014794 superficial urinary bladder carcinoma Diseases 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011285 therapeutic regimen Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 208000014001 urinary system disease Diseases 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 101150000874 11 gene Proteins 0.000 description 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
- 101150005896 59 gene Proteins 0.000 description 1
- USVMJSALORZVDV-UHFFFAOYSA-N 6-(gamma,gamma-dimethylallylamino)purine riboside Natural products C1=NC=2C(NCC=C(C)C)=NC=NC=2N1C1OC(CO)C(O)C1O USVMJSALORZVDV-UHFFFAOYSA-N 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 101100263837 Bovine ephemeral fever virus (strain BB7721) beta gene Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010008723 Chondrodystrophy Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 230000008836 DNA modification Effects 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 101100316840 Enterobacteria phage P4 Beta gene Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 102100040870 Glycine amidinotransferase, mitochondrial Human genes 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical group C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000737574 Homo sapiens Complement factor H Proteins 0.000 description 1
- 101000893303 Homo sapiens Glycine amidinotransferase, mitochondrial Proteins 0.000 description 1
- 101001123334 Homo sapiens Proteoglycan 3 Proteins 0.000 description 1
- 206010020524 Hydronephrosis Diseases 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 208000015924 Lithiasis Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000006890 Methyl-CpG-Binding Protein 2 Human genes 0.000 description 1
- 108010072388 Methyl-CpG-Binding Protein 2 Proteins 0.000 description 1
- 108700028031 Myelin Basic Proteins 0.000 description 1
- USVMJSALORZVDV-SDBHATRESA-N N(6)-(Delta(2)-isopentenyl)adenosine Chemical compound C1=NC=2C(NCC=C(C)C)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O USVMJSALORZVDV-SDBHATRESA-N 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108010035916 Nuclear Matrix-Associated Proteins Proteins 0.000 description 1
- 102000008297 Nuclear Matrix-Associated Proteins Human genes 0.000 description 1
- 101150080012 OSMR gene Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 238000002944 PCR assay Methods 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- ZYFVNVRFVHJEIU-UHFFFAOYSA-N PicoGreen Chemical compound CN(C)CCCN(CCCN(C)C)C1=CC(=CC2=[N+](C3=CC=CC=C3S2)C)C2=CC=CC=C2N1C1=CC=CC=C1 ZYFVNVRFVHJEIU-UHFFFAOYSA-N 0.000 description 1
- 208000032236 Predisposition to disease Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102100023320 Ral guanine nucleotide dissociation stimulator Human genes 0.000 description 1
- 108050008437 Ral guanine nucleotide dissociation stimulator Proteins 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 102100030852 Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Human genes 0.000 description 1
- 101710179516 Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Proteins 0.000 description 1
- CGNLCCVKSWNSDG-UHFFFAOYSA-N SYBR Green I Chemical compound CN(C)CCCN(CCC)C1=CC(C=C2N(C3=CC=CC=C3S2)C)=C2C=CC=CC2=[N+]1C1=CC=CC=C1 CGNLCCVKSWNSDG-UHFFFAOYSA-N 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 101150094002 TWIST1 gene Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Chemical class Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 208000008919 achondroplasia Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000000137 annealing Methods 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
- 239000002543 antimycotic Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 210000003567 ascitic fluid Anatomy 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000003196 chaotropic effect Effects 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000001268 chyle Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007608 epigenetic mechanism Effects 0.000 description 1
- 230000006565 epigenetic process Effects 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 238000003154 fluorescent dye transfer Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012520 frozen sample Substances 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 238000013412 genome amplification Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 238000012203 high throughput assay Methods 0.000 description 1
- 102000045512 human CFH Human genes 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004880 lymph fluid Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000007403 mPCR Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000012775 microarray technology Methods 0.000 description 1
- 210000000479 mitotic spindle apparatus Anatomy 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 108010008217 nidogen Proteins 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 231100001221 nontumorigenic Toxicity 0.000 description 1
- 210000000299 nuclear matrix Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 201000005737 orchitis Diseases 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000002974 pharmacogenomic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 210000004910 pleural fluid Anatomy 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000000039 preparative column chromatography Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000012175 pyrosequencing Methods 0.000 description 1
- 238000012205 qualitative assay Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- JNMWHTHYDQTDQZ-UHFFFAOYSA-N selenium sulfide Chemical compound S=[Se]=S JNMWHTHYDQTDQZ-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 201000003896 thanatophoric dysplasia Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 210000003741 urothelium Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/112—Disease subtyping, staging or classification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/154—Methylation markers
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96012907P | 2007-09-17 | 2007-09-17 | |
| US7197108P | 2008-05-28 | 2008-05-28 | |
| PCT/GB2008/002093 WO2008155549A2 (en) | 2007-06-19 | 2008-06-19 | Improved urine sample collecting and processing |
| PCT/EP2008/007465 WO2009036922A2 (en) | 2007-09-17 | 2008-09-11 | Novel markers for bladder cancer detection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2198042T3 true DK2198042T3 (en) | 2017-01-23 |
Family
ID=39945563
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK08802026.8T DK2198042T3 (en) | 2007-09-17 | 2008-09-11 | New markers for bladder cancer detection |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9322065B2 (https=) |
| EP (2) | EP2198042B1 (https=) |
| JP (2) | JP5697448B2 (https=) |
| CA (1) | CA2699606C (https=) |
| DK (1) | DK2198042T3 (https=) |
| ES (1) | ES2605237T3 (https=) |
| PL (1) | PL2198042T3 (https=) |
| WO (1) | WO2009036922A2 (https=) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101353695B (zh) * | 2007-07-23 | 2013-05-01 | 上海市肿瘤研究所 | 尿沉淀dna甲基化谱式分析诊断膀胱癌的方法和试剂盒 |
| EP2198042B1 (en) * | 2007-09-17 | 2016-11-02 | MDxHealth SA | Novel markers for bladder cancer detection |
| CA2755358A1 (en) | 2009-03-13 | 2010-09-16 | Mdxhealth Sa | Novel markers for bladder cancer detection |
| WO2010113529A1 (ja) * | 2009-04-03 | 2010-10-07 | 国立大学法人山口大学 | 大腸腫瘍の検出方法 |
| ES2721424T3 (es) * | 2009-04-20 | 2019-07-31 | Univ Erasmus Med Ct Rotterdam | Método de diagnóstico del cáncer de vejiga |
| EP2966181B1 (en) * | 2009-06-26 | 2018-02-14 | Epigenomics AG | Methods and nucleic acids for analysis of bladder carcinoma |
| US9752187B2 (en) | 2009-12-11 | 2017-09-05 | Nucleix | Categorization of DNA samples |
| US9783850B2 (en) | 2010-02-19 | 2017-10-10 | Nucleix | Identification of source of DNA samples |
| WO2011104731A1 (en) * | 2010-02-26 | 2011-09-01 | Decode Genetics Ehf | Genetic variants as markers for use in urinary bladder cancer risk assessment, diagnosis, prognosis and treatment |
| WO2011112880A2 (en) * | 2010-03-12 | 2011-09-15 | The Johns Hopkins University | Hypermethylation biomarkers for detection of head and neck squamous cell cancer |
| US20130041047A1 (en) * | 2011-06-01 | 2013-02-14 | Aros Applied Biotechnology As | Urinary Methylation Markers for Bladder Cancer |
| WO2015035415A1 (en) | 2013-09-09 | 2015-03-12 | Nantomics, Llc | Method of detecting suceptibility to breast cancer through mutations in the fgfr3 and tp53 genes |
| US10689652B2 (en) | 2013-10-02 | 2020-06-23 | The Regents Of The University Of California | Methods for immortalization of epithelial cells |
| US9476100B1 (en) | 2015-07-06 | 2016-10-25 | Nucleix Ltd. | Methods for diagnosing bladder cancer |
| DE102015009187B3 (de) | 2015-07-16 | 2016-10-13 | Dimo Dietrich | Verfahren zur Bestimmung einer Mutation in genomischer DNA, Verwendung des Verfahrens und Kit zur Durchführung des Verfahrens |
| WO2017062517A1 (en) * | 2015-10-06 | 2017-04-13 | The Regents Of The University Of California | Non-coding rnas linked to immortality and associated methods and compositions |
| CN115418401A (zh) * | 2015-10-08 | 2022-12-02 | 会聚基因学有限公司 | 用于膀胱癌的尿监测的诊断测定 |
| RU2612139C1 (ru) * | 2015-12-29 | 2017-03-02 | Федеральное государственное бюджетное учреждение науки институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук (ИБХ РАН) | Набор синтетических олигонуклеотидов для определения уровней экспрессии гена pdlim4 |
| CN109072310A (zh) * | 2016-04-01 | 2018-12-21 | 纳诺梅德诊断私人有限公司 | 在尿液中检测癌症 |
| US12258632B2 (en) | 2016-07-06 | 2025-03-25 | Case Western Reserve University | Methods and compositions for detecting esophageal neoplasias and/or metaplasias in the esophagus |
| WO2018047883A1 (ja) * | 2016-09-06 | 2018-03-15 | 株式会社ユカシカド | スポット尿を用いたヘルスケアシステム |
| KR20190054086A (ko) * | 2016-09-29 | 2019-05-21 | 이에이 파마 가부시키가이샤 | 고발성 대장암 발증 가능성의 판정 방법 |
| CN107014658B (zh) * | 2017-05-27 | 2023-08-25 | 四川省肿瘤医院 | 提取游离细胞的方法及试剂盒 |
| BR112020001091A2 (pt) * | 2017-08-02 | 2020-09-15 | Sarstedt Ag & Co. Kg | processo e composição para a estabilização de ácidos nucleicos livres de células |
| EP3821038A1 (en) * | 2018-07-11 | 2021-05-19 | Stichting VUmc | Urine dna methylation markers for bladder cancer |
| IL265451B (en) | 2019-03-18 | 2020-01-30 | Frumkin Dan | Methods and systems for the detection of methylation changes in DNA samples |
| KR102186534B1 (ko) * | 2019-04-11 | 2020-12-03 | 차의과학대학교 산학협력단 | 수지상세포의 성숙도 측정 방법 및 조성물, 그리고 이의 용도 |
| CN110283914A (zh) * | 2019-07-29 | 2019-09-27 | 上海透景生命科技股份有限公司 | 一种膀胱癌的新型基因诊断试剂盒及其应用 |
| CN113943799B (zh) * | 2020-07-16 | 2023-12-15 | 广州达健生物科技有限公司 | 用于检测膀胱癌的组合物及其试剂盒和应用 |
| CN113957160B (zh) * | 2020-07-20 | 2024-03-29 | 深圳华大生命科学研究院 | 检测膀胱癌的标志物及检测该标志物的引物对及其应用 |
| CN115094139B (zh) * | 2022-06-22 | 2023-04-28 | 武汉艾米森生命科技有限公司 | 检测甲基化水平的试剂在制备膀胱癌诊断产品中的应用以及膀胱癌诊断试剂盒 |
| CN116004831B (zh) * | 2023-01-05 | 2024-10-01 | 武汉艾米森生命科技有限公司 | 一种用于膀胱癌的诊断或辅助诊断的试剂及检测试剂盒 |
| US20240271221A1 (en) * | 2023-01-20 | 2024-08-15 | Grail, Llc | Methods for analysis of cell-free nucleic acids in urine |
| CN117265114A (zh) * | 2023-10-13 | 2023-12-22 | 青岛瑞思德医学检验实验室有限公司 | 一种膀胱癌检测试剂盒及检测方法 |
| CN119331973A (zh) * | 2024-10-17 | 2025-01-21 | 南京科佰生物科技有限公司 | Twist1基因甲基化检测引物探针体系及其试剂盒 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4437975A (en) | 1977-07-20 | 1984-03-20 | Mobil Oil Corporation | Manufacture of lube base stock oil |
| WO1989001050A1 (en) | 1987-07-31 | 1989-02-09 | The Board Of Trustees Of The Leland Stanford Junior University | Selective amplification of target polynucleotide sequences |
| CA2005589C (en) | 1988-12-16 | 2001-02-06 | Akzo Nobel Nv | Self-sustained, sequence replication system |
| US6017704A (en) | 1996-06-03 | 2000-01-25 | The Johns Hopkins University School Of Medicine | Method of detection of methylated nucleic acid using agents which modify unmethylated cytosine and distinguishing modified methylated and non-methylated nucleic acids |
| GB9710995D0 (en) * | 1997-05-28 | 1997-07-23 | Marie Curie Research Inst | Tumour suppressor locus and gene at 9q32-33 |
| AU766084B2 (en) * | 1998-10-19 | 2003-10-09 | Methylgene, Inc. | Modulation of gene expression by combination therapy |
| KR100475649B1 (ko) * | 2001-01-29 | 2005-03-10 | 배석철 | 항암활성을 나타내는 ｒｕｎｘ３ 유전자 및 그의 용도 |
| JP2005535283A (ja) | 2001-11-13 | 2005-11-24 | ルビコン ゲノミクス インコーポレイテッド | ランダムフラグメント化により生成されたｄｎａ分子を用いたｄｎａ増幅および配列決定 |
| WO2004067726A2 (en) | 2003-01-29 | 2004-08-12 | Keck Graduate Institute | Isothermal reactions for the amplification of oligonucleotides |
| US20040209299A1 (en) | 2003-03-07 | 2004-10-21 | Rubicon Genomics, Inc. | In vitro DNA immortalization and whole genome amplification using libraries generated from randomly fragmented DNA |
| EP1604040B1 (en) | 2003-03-07 | 2010-10-13 | Rubicon Genomics, Inc. | Amplification and analysis of whole genome and whole transcriptome libraries generated by a dna polymerization process |
| US8062849B2 (en) * | 2003-10-28 | 2011-11-22 | The Johns Hopkins University | Quantitative multiplex methylation-specific PCR |
| JP4590893B2 (ja) | 2004-03-23 | 2010-12-01 | Ｊｓｒ株式会社 | 接着剤用液状硬化性樹脂組成物 |
| EP2386654A1 (en) * | 2005-05-02 | 2011-11-16 | University of Southern California | DNA Methylation markers associated with the CpG island methylator phenotype (cimp) in human colorectal cancer |
| US20070099209A1 (en) | 2005-06-13 | 2007-05-03 | The Regents Of The University Of Michigan | Compositions and methods for treating and diagnosing cancer |
| WO2007072225A2 (en) | 2005-12-01 | 2007-06-28 | Medical Prognosis Institute | Methods and devices for identifying biomarkers of treatment response and use thereof to predict treatment efficacy |
| WO2007116417A1 (en) | 2006-04-07 | 2007-10-18 | Silvia Sabbioni | Novel dna methylation markers useful for the diagnosis of neoplastic diseases |
| EP2173897A2 (en) * | 2007-06-19 | 2010-04-14 | Oncomethylome Sciences SA | Improved urine sample collecting and processing |
| EP2198042B1 (en) * | 2007-09-17 | 2016-11-02 | MDxHealth SA | Novel markers for bladder cancer detection |
-
2008
- 2008-09-11 EP EP08802026.8A patent/EP2198042B1/en active Active
- 2008-09-11 EP EP16196638.7A patent/EP3147375A1/en not_active Withdrawn
- 2008-09-11 US US12/678,696 patent/US9322065B2/en active Active
- 2008-09-11 DK DK08802026.8T patent/DK2198042T3/en active
- 2008-09-11 PL PL08802026T patent/PL2198042T3/pl unknown
- 2008-09-11 ES ES08802026.8T patent/ES2605237T3/es active Active
- 2008-09-11 JP JP2010524399A patent/JP5697448B2/ja active Active
- 2008-09-11 WO PCT/EP2008/007465 patent/WO2009036922A2/en not_active Ceased
- 2008-09-11 CA CA2699606A patent/CA2699606C/en active Active
-
2014
- 2014-10-09 JP JP2014208231A patent/JP2015051006A/ja active Pending
-
2016
- 2016-03-24 US US15/079,948 patent/US10113202B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CA2699606A1 (en) | 2009-03-26 |
| EP3147375A1 (en) | 2017-03-29 |
| WO2009036922A2 (en) | 2009-03-26 |
| US9322065B2 (en) | 2016-04-26 |
| JP2015051006A (ja) | 2015-03-19 |
| US20100280134A1 (en) | 2010-11-04 |
| US10113202B2 (en) | 2018-10-30 |
| JP5697448B2 (ja) | 2015-04-08 |
| JP2010538624A (ja) | 2010-12-16 |
| EP2198042B1 (en) | 2016-11-02 |
| ES2605237T3 (es) | 2017-03-13 |
| EP2198042A2 (en) | 2010-06-23 |
| CA2699606C (en) | 2023-04-11 |
| US20160208341A1 (en) | 2016-07-21 |
| PL2198042T3 (pl) | 2017-05-31 |
| WO2009036922A3 (en) | 2009-05-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK2198042T3 (en) | New markers for bladder cancer detection | |
| US11987848B2 (en) | Fecal sample processing and analysis comprising detection of blood | |
| US12215389B2 (en) | Compositions for detecting epigenetic modifications | |
| US20110117551A1 (en) | Detection and prognosis of lung cancer | |
| WO2009108917A2 (en) | Markers for improved detection of breast cancer | |
| JP2022536846A (ja) | 胃癌を診断するための高メチル化遺伝子の検出 | |
| US20140141998A1 (en) | Neoplasia screening compositions and methods of use | |
| US8617809B2 (en) | Neoplasia screening compositions and methods of use | |
| US9388471B2 (en) | Methylation of the GATA4 gene in urine samples as a marker for bladder cancer detection |