CA2702653A1 - Diagnostic, predictive and prognostic testing for cancer - Google Patents
Diagnostic, predictive and prognostic testing for cancer Download PDFInfo
- Publication number
- CA2702653A1 CA2702653A1 CA2702653A CA2702653A CA2702653A1 CA 2702653 A1 CA2702653 A1 CA 2702653A1 CA 2702653 A CA2702653 A CA 2702653A CA 2702653 A CA2702653 A CA 2702653A CA 2702653 A1 CA2702653 A1 CA 2702653A1
- Authority
- CA
- Canada
- Prior art keywords
- cancer
- biomarker
- level
- aurora
- subject
- 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.)
- Abandoned
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 243
- 201000011510 cancer Diseases 0.000 title claims abstract description 76
- 238000012360 testing method Methods 0.000 title description 26
- 239000000090 biomarker Substances 0.000 claims abstract description 246
- 102000004064 Geminin Human genes 0.000 claims abstract description 123
- 108090000577 Geminin Proteins 0.000 claims abstract description 123
- 238000000034 method Methods 0.000 claims abstract description 110
- 239000012472 biological sample Substances 0.000 claims abstract description 35
- 238000011282 treatment Methods 0.000 claims abstract description 26
- 238000004393 prognosis Methods 0.000 claims abstract description 15
- 238000011269 treatment regimen Methods 0.000 claims abstract description 11
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 10
- 210000004027 cell Anatomy 0.000 claims description 134
- 230000022131 cell cycle Effects 0.000 claims description 98
- 101100533947 Mus musculus Serpina3k gene Proteins 0.000 claims description 71
- 101150070711 mcm2 gene Proteins 0.000 claims description 71
- -1 Aurora A Proteins 0.000 claims description 48
- 238000004458 analytical method Methods 0.000 claims description 46
- 210000001519 tissue Anatomy 0.000 claims description 41
- 206010006187 Breast cancer Diseases 0.000 claims description 39
- 208000026310 Breast neoplasm Diseases 0.000 claims description 39
- 108010056274 polo-like kinase 1 Proteins 0.000 claims description 31
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 26
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 claims description 20
- 101100520072 Caenorhabditis elegans pik-1 gene Proteins 0.000 claims description 17
- 238000001514 detection method Methods 0.000 claims description 16
- 206010033128 Ovarian cancer Diseases 0.000 claims description 15
- 238000001574 biopsy Methods 0.000 claims description 15
- 238000003556 assay Methods 0.000 claims description 12
- 239000002246 antineoplastic agent Substances 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 10
- 150000007523 nucleic acids Chemical group 0.000 claims description 9
- 230000003321 amplification Effects 0.000 claims description 8
- 229940127089 cytotoxic agent Drugs 0.000 claims description 8
- 238000002493 microarray Methods 0.000 claims description 8
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 8
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 238000010324 immunological assay Methods 0.000 claims description 7
- 238000001356 surgical procedure Methods 0.000 claims description 7
- 238000012544 monitoring process Methods 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- 210000002700 urine Anatomy 0.000 claims description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 5
- 238000009595 pap smear Methods 0.000 claims description 5
- 238000003757 reverse transcription PCR Methods 0.000 claims description 5
- 238000002965 ELISA Methods 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 238000000636 Northern blotting Methods 0.000 claims description 4
- 206010036790 Productive cough Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 238000002105 Southern blotting Methods 0.000 claims description 4
- 230000001680 brushing effect Effects 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 239000011159 matrix material Substances 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 210000002966 serum Anatomy 0.000 claims description 4
- 210000003802 sputum Anatomy 0.000 claims description 4
- 208000024794 sputum Diseases 0.000 claims description 4
- 238000013518 transcription Methods 0.000 claims description 4
- 230000035897 transcription Effects 0.000 claims description 4
- 238000001262 western blot Methods 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims 6
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 6
- 201000005112 urinary bladder cancer Diseases 0.000 claims 6
- 206010009944 Colon cancer Diseases 0.000 claims 3
- 206010014733 Endometrial cancer Diseases 0.000 claims 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 3
- 208000000453 Skin Neoplasms Diseases 0.000 claims 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 3
- 208000023915 Ureteral Neoplasms Diseases 0.000 claims 3
- 210000004556 brain Anatomy 0.000 claims 3
- 208000029742 colonic neoplasm Diseases 0.000 claims 3
- 206010017758 gastric cancer Diseases 0.000 claims 3
- 201000005202 lung cancer Diseases 0.000 claims 3
- 208000020816 lung neoplasm Diseases 0.000 claims 3
- 210000002200 mouth mucosa Anatomy 0.000 claims 3
- 210000002381 plasma Anatomy 0.000 claims 3
- 201000000849 skin cancer Diseases 0.000 claims 3
- 201000011549 stomach cancer Diseases 0.000 claims 3
- 230000014509 gene expression Effects 0.000 description 78
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 51
- 230000004083 survival effect Effects 0.000 description 50
- 201000010099 disease Diseases 0.000 description 49
- 108090000623 proteins and genes Proteins 0.000 description 45
- 239000000523 sample Substances 0.000 description 40
- 230000002062 proliferating effect Effects 0.000 description 31
- 230000006369 cell cycle progression Effects 0.000 description 30
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 28
- 239000005441 aurora Substances 0.000 description 28
- 102000004169 proteins and genes Human genes 0.000 description 28
- 230000034614 regulation of DNA-dependent DNA replication initiation Effects 0.000 description 25
- 230000000394 mitotic effect Effects 0.000 description 23
- 229920001184 polypeptide Polymers 0.000 description 23
- 102000004196 processed proteins & peptides Human genes 0.000 description 23
- 108020004414 DNA Proteins 0.000 description 21
- 210000004881 tumor cell Anatomy 0.000 description 21
- 102000003989 Aurora kinases Human genes 0.000 description 18
- 108090000433 Aurora kinases Proteins 0.000 description 18
- 102000001253 Protein Kinase Human genes 0.000 description 18
- 208000036878 aneuploidy Diseases 0.000 description 18
- 230000018486 cell cycle phase Effects 0.000 description 18
- 230000001351 cycling effect Effects 0.000 description 17
- 230000035755 proliferation Effects 0.000 description 17
- 230000009870 specific binding Effects 0.000 description 17
- 101000582926 Dictyostelium discoideum Probable serine/threonine-protein kinase PLK Proteins 0.000 description 16
- 230000004069 differentiation Effects 0.000 description 16
- 238000002372 labelling Methods 0.000 description 16
- 239000003550 marker Substances 0.000 description 16
- 230000005856 abnormality Effects 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 230000018199 S phase Effects 0.000 description 13
- 230000003322 aneuploid effect Effects 0.000 description 13
- 230000004663 cell proliferation Effects 0.000 description 13
- 238000009509 drug development Methods 0.000 description 13
- 208000031448 Genomic Instability Diseases 0.000 description 12
- 108010033040 Histones Proteins 0.000 description 12
- 230000027455 binding Effects 0.000 description 12
- 230000010261 cell growth Effects 0.000 description 12
- 238000011527 multiparameter analysis Methods 0.000 description 12
- 210000000481 breast Anatomy 0.000 description 11
- 238000009826 distribution Methods 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 230000011278 mitosis Effects 0.000 description 11
- 230000037361 pathway Effects 0.000 description 11
- 108050006400 Cyclin Proteins 0.000 description 10
- 102000006947 Histones Human genes 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 101150029707 ERBB2 gene Proteins 0.000 description 9
- 230000002159 abnormal effect Effects 0.000 description 9
- 230000034994 death Effects 0.000 description 9
- 231100000517 death Toxicity 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000008482 dysregulation Effects 0.000 description 9
- 230000012010 growth Effects 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 102000016736 Cyclin Human genes 0.000 description 8
- 230000003111 delayed effect Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000000470 constituent Substances 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 238000001325 log-rank test Methods 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 230000002018 overexpression Effects 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 230000007704 transition Effects 0.000 description 7
- 230000027311 M phase Effects 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000008267 milk Substances 0.000 description 6
- 210000004080 milk Anatomy 0.000 description 6
- 235000013336 milk Nutrition 0.000 description 6
- 238000000491 multivariate analysis Methods 0.000 description 6
- 102000020233 phosphotransferase Human genes 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000007473 univariate analysis Methods 0.000 description 6
- 208000000058 Anaplasia Diseases 0.000 description 5
- 230000004543 DNA replication Effects 0.000 description 5
- 230000010190 G1 phase Effects 0.000 description 5
- 231100001075 aneuploidy Toxicity 0.000 description 5
- 231100000504 carcinogenesis Toxicity 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000003119 immunoblot Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 239000003226 mitogen Substances 0.000 description 5
- 230000002611 ovarian Effects 0.000 description 5
- 108060006633 protein kinase Proteins 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 230000001360 synchronised effect Effects 0.000 description 5
- 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 4
- 108010077544 Chromatin Proteins 0.000 description 4
- 206010058314 Dysplasia Diseases 0.000 description 4
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 4
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 238000011226 adjuvant chemotherapy Methods 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 239000013592 cell lysate Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 210000003483 chromatin Anatomy 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000010195 expression analysis Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 230000002962 histologic effect Effects 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 230000009826 neoplastic cell growth Effects 0.000 description 4
- 238000012758 nuclear staining Methods 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 210000001672 ovary Anatomy 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 230000005855 radiation Effects 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 230000008093 supporting effect Effects 0.000 description 4
- 230000004797 therapeutic response Effects 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 210000003932 urinary bladder Anatomy 0.000 description 4
- 101100456282 Caenorhabditis elegans mcm-4 gene Proteins 0.000 description 3
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 3
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 3
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 3
- 102100037854 G1/S-specific cyclin-E2 Human genes 0.000 description 3
- 101000738575 Homo sapiens G1/S-specific cyclin-E2 Proteins 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- 101150004492 Mcm3 gene Proteins 0.000 description 3
- 101150088918 Mcm6 gene Proteins 0.000 description 3
- 101150023098 Mcm7 gene Proteins 0.000 description 3
- 102000016304 Origin Recognition Complex Human genes 0.000 description 3
- 108010067244 Origin Recognition Complex Proteins 0.000 description 3
- 102000000505 Ribonucleotide Reductases Human genes 0.000 description 3
- 108010041388 Ribonucleotide Reductases Proteins 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 108010022394 Threonine synthase Proteins 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 210000003679 cervix uteri Anatomy 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 3
- 229960005420 etoposide Drugs 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000009397 lymphovascular invasion Effects 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 108010047866 ribonucleotide reductase M2 Proteins 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000010200 validation analysis Methods 0.000 description 3
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 2
- 102100032306 Aurora kinase B Human genes 0.000 description 2
- 108090000749 Aurora kinase B Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 102000003909 Cyclin E Human genes 0.000 description 2
- 108090000257 Cyclin E Proteins 0.000 description 2
- 108010009367 Cyclin-Dependent Kinase Inhibitor p18 Proteins 0.000 description 2
- 102000009503 Cyclin-Dependent Kinase Inhibitor p18 Human genes 0.000 description 2
- 102000016559 DNA Primase Human genes 0.000 description 2
- 108010092681 DNA Primase Proteins 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- 101710148291 DNA ligase 1 Proteins 0.000 description 2
- 102100029995 DNA ligase 1 Human genes 0.000 description 2
- 102100028862 Delta-aminolevulinic acid dehydratase Human genes 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 108010093502 E2F Transcription Factors Proteins 0.000 description 2
- 102000001388 E2F Transcription Factors Human genes 0.000 description 2
- 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 2
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108091008794 FGF receptors Proteins 0.000 description 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
- 101000886596 Homo sapiens Geminin Proteins 0.000 description 2
- 101000624625 Homo sapiens M-phase inducer phosphatase 1 Proteins 0.000 description 2
- 101000896657 Homo sapiens Mitotic checkpoint serine/threonine-protein kinase BUB1 Proteins 0.000 description 2
- 101000945496 Homo sapiens Proliferation marker protein Ki-67 Proteins 0.000 description 2
- 101001092206 Homo sapiens Replication protein A 32 kDa subunit Proteins 0.000 description 2
- 101000904152 Homo sapiens Transcription factor E2F1 Proteins 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 2
- 102100037611 Lysophospholipase Human genes 0.000 description 2
- 102100023326 M-phase inducer phosphatase 1 Human genes 0.000 description 2
- 238000000585 Mann–Whitney U test Methods 0.000 description 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- 102100021691 Mitotic checkpoint serine/threonine-protein kinase BUB1 Human genes 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102100024315 Pericentrin Human genes 0.000 description 2
- 101710179262 Pericentrin Proteins 0.000 description 2
- 108010058864 Phospholipases A2 Proteins 0.000 description 2
- 208000020584 Polyploidy Diseases 0.000 description 2
- 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 2
- 102100034836 Proliferation marker protein Ki-67 Human genes 0.000 description 2
- 108010068097 Rad51 Recombinase Proteins 0.000 description 2
- 102000002490 Rad51 Recombinase Human genes 0.000 description 2
- 101710147937 Replication factor C subunit 4 Proteins 0.000 description 2
- 102100035525 Replication protein A 32 kDa subunit Human genes 0.000 description 2
- 238000003646 Spearman's rank correlation coefficient Methods 0.000 description 2
- 108010071698 Spermine synthase Proteins 0.000 description 2
- 102100037616 Spermine synthase Human genes 0.000 description 2
- 208000035199 Tetraploidy Diseases 0.000 description 2
- 102100024026 Transcription factor E2F1 Human genes 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- OGNYUTNQZVRGMN-UHFFFAOYSA-N ZM447439 Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 OGNYUTNQZVRGMN-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 208000037842 advanced-stage tumor Diseases 0.000 description 2
- 229950010817 alvocidib Drugs 0.000 description 2
- BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 230000023359 cell cycle switching, meiotic to mitotic cell cycle Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000003793 centrosome Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- 210000004953 colonic tissue Anatomy 0.000 description 2
- 238000004163 cytometry Methods 0.000 description 2
- 238000012303 cytoplasmic staining Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 2
- 229960001904 epirubicin Drugs 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- QTTMOCOWZLSYSV-QWAPEVOJSA-M equilin sodium sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4C3=CCC2=C1 QTTMOCOWZLSYSV-QWAPEVOJSA-M 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 102000054910 human GMNN Human genes 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000003365 immunocytochemistry Methods 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 208000030776 invasive breast carcinoma Diseases 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 230000036456 mitotic arrest Effects 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 239000012120 mounting media Substances 0.000 description 2
- 210000005170 neoplastic cell Anatomy 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000005204 segregation Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 2
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 230000003319 supportive effect Effects 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 238000011870 unpaired t-test Methods 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- AFWRJOYNLMVZQO-GMFATLNBSA-N (1r,2r,4as,8as)-1-[(1e,3e)-5-hydroxy-3-methylpenta-1,3-dienyl]-2,5,5,8a-tetramethyl-3,4,4a,6,7,8-hexahydro-1h-naphthalen-2-ol Chemical compound CC1(C)CCC[C@]2(C)[C@@H](/C=C/C(=C/CO)/C)[C@](C)(O)CC[C@H]21 AFWRJOYNLMVZQO-GMFATLNBSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- WKKCYLSCLQVWFD-UHFFFAOYSA-N 1,2-dihydropyrimidin-4-amine Chemical compound N=C1NCNC=C1 WKKCYLSCLQVWFD-UHFFFAOYSA-N 0.000 description 1
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- WVKOPZMDOFGFAK-UHFFFAOYSA-N 4-hydroperoxycyclophosphamide Chemical compound OOC1=NP(O)(N(CCCl)CCCl)OCC1 WVKOPZMDOFGFAK-UHFFFAOYSA-N 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- PBCZSGKMGDDXIJ-HQCWYSJUSA-N 7-hydroxystaurosporine Chemical compound N([C@H](O)C1=C2C3=CC=CC=C3N3C2=C24)C(=O)C1=C2C1=CC=CC=C1N4[C@H]1C[C@@H](NC)[C@@H](OC)[C@]3(C)O1 PBCZSGKMGDDXIJ-HQCWYSJUSA-N 0.000 description 1
- PBCZSGKMGDDXIJ-UHFFFAOYSA-N 7beta-hydroxystaurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3C(O)NC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 PBCZSGKMGDDXIJ-UHFFFAOYSA-N 0.000 description 1
- 102100025339 ATP-dependent DNA helicase DDX11 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000052587 Anaphase-Promoting Complex-Cyclosome Apc3 Subunit Human genes 0.000 description 1
- 108700004606 Anaphase-Promoting Complex-Cyclosome Apc3 Subunit Proteins 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 102100034524 Apoptotic protease-activating factor 1 Human genes 0.000 description 1
- 101100467538 Arabidopsis thaliana RANBPM gene Proteins 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 108090000461 Aurora Kinase A Proteins 0.000 description 1
- 102100032311 Aurora kinase A Human genes 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 102000036365 BRCA1 Human genes 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 108700020462 BRCA2 Proteins 0.000 description 1
- 102000052609 BRCA2 Human genes 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
- 108010006654 Bleomycin Proteins 0.000 description 1
- 102000008143 Bone Morphogenetic Protein 2 Human genes 0.000 description 1
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 1
- 108010040422 Bone Morphogenetic Protein Receptors Proteins 0.000 description 1
- 102000001893 Bone Morphogenetic Protein Receptors Human genes 0.000 description 1
- 101150008921 Brca2 gene Proteins 0.000 description 1
- 102000001805 Bromodomains Human genes 0.000 description 1
- 108050009021 Bromodomains Proteins 0.000 description 1
- 102100035793 CD83 antigen Human genes 0.000 description 1
- 101150108242 CDC27 gene Proteins 0.000 description 1
- 108091007914 CDKs Proteins 0.000 description 1
- 101100411918 Camellia sinensis pRB gene Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102000003952 Caspase 3 Human genes 0.000 description 1
- 102100024490 Cdc42 effector protein 3 Human genes 0.000 description 1
- 101710109268 Cdc42 effector protein 3 Proteins 0.000 description 1
- 102100025053 Cell division control protein 45 homolog Human genes 0.000 description 1
- 102100027047 Cell division control protein 6 homolog Human genes 0.000 description 1
- 102100020736 Chromosome-associated kinesin KIF4A Human genes 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 206010065163 Clonal evolution Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 1
- 102000010970 Connexin Human genes 0.000 description 1
- 108050001175 Connexin Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 108010060273 Cyclin A2 Proteins 0.000 description 1
- 108010060387 Cyclin B2 Proteins 0.000 description 1
- 102000003910 Cyclin D Human genes 0.000 description 1
- 108090000259 Cyclin D Proteins 0.000 description 1
- 108010058545 Cyclin D3 Proteins 0.000 description 1
- 102100025191 Cyclin-A2 Human genes 0.000 description 1
- 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 1
- 108010017222 Cyclin-Dependent Kinase Inhibitor p57 Proteins 0.000 description 1
- 102000004480 Cyclin-Dependent Kinase Inhibitor p57 Human genes 0.000 description 1
- 102100038250 Cyclin-G2 Human genes 0.000 description 1
- 102100036329 Cyclin-dependent kinase 3 Human genes 0.000 description 1
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 108090000133 DNA helicases Proteins 0.000 description 1
- 102000003844 DNA helicases Human genes 0.000 description 1
- 102100034157 DNA mismatch repair protein Msh2 Human genes 0.000 description 1
- 102100024829 DNA polymerase delta catalytic subunit Human genes 0.000 description 1
- 101710087290 DNA primase small subunit Proteins 0.000 description 1
- 102100040792 DNA primase small subunit Human genes 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
- 101100239628 Danio rerio myca gene Proteins 0.000 description 1
- 101100216227 Dictyostelium discoideum anapc3 gene Proteins 0.000 description 1
- 101710155964 Diuretic hormone 1 Proteins 0.000 description 1
- 101001084710 Drosophila melanogaster Histone H2A.v Proteins 0.000 description 1
- 102100027275 Dual specificity protein phosphatase 7 Human genes 0.000 description 1
- 108700037629 ETS-related transcription factor Elf-4 Proteins 0.000 description 1
- 102100039247 ETS-related transcription factor Elf-4 Human genes 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000048186 Endothelin-converting enzyme 1 Human genes 0.000 description 1
- 108030001679 Endothelin-converting enzyme 1 Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102100021381 Eukaryotic translation elongation factor 1 epsilon-1 Human genes 0.000 description 1
- 201000004939 Fanconi anemia Diseases 0.000 description 1
- 102000004150 Flap endonucleases Human genes 0.000 description 1
- 108090000652 Flap endonucleases Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 102000016970 Follistatin Human genes 0.000 description 1
- 108010014612 Follistatin Proteins 0.000 description 1
- 102100037859 G1/S-specific cyclin-D3 Human genes 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- 102100033201 G2/mitotic-specific cyclin-B2 Human genes 0.000 description 1
- 241001032544 Galearctus aurora Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 206010066476 Haematological malignancy Diseases 0.000 description 1
- 102100022128 High mobility group protein B2 Human genes 0.000 description 1
- 102000017286 Histone H2A Human genes 0.000 description 1
- 108050005231 Histone H2A Proteins 0.000 description 1
- 102100023919 Histone H2A.Z Human genes 0.000 description 1
- 101710103773 Histone H2B Proteins 0.000 description 1
- 102100021639 Histone H2B type 1-K Human genes 0.000 description 1
- 108091006823 Homeobox A10 Proteins Proteins 0.000 description 1
- 102000037315 Homeobox A10 Proteins Human genes 0.000 description 1
- 102100022650 Homeobox protein Hox-A7 Human genes 0.000 description 1
- 102100021090 Homeobox protein Hox-A9 Human genes 0.000 description 1
- 102000009331 Homeodomain Proteins Human genes 0.000 description 1
- 108010048671 Homeodomain Proteins Proteins 0.000 description 1
- 101000722210 Homo sapiens ATP-dependent DNA helicase DDX11 Proteins 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000924629 Homo sapiens Apoptotic protease-activating factor 1 Proteins 0.000 description 1
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 1
- 101000934421 Homo sapiens Cell division control protein 45 homolog Proteins 0.000 description 1
- 101000914465 Homo sapiens Cell division control protein 6 homolog Proteins 0.000 description 1
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 1
- 101001139157 Homo sapiens Chromosome-associated kinesin KIF4A Proteins 0.000 description 1
- 101000884216 Homo sapiens Cyclin-G2 Proteins 0.000 description 1
- 101000868333 Homo sapiens Cyclin-dependent kinase 1 Proteins 0.000 description 1
- 101000945639 Homo sapiens Cyclin-dependent kinase inhibitor 3 Proteins 0.000 description 1
- 101001134036 Homo sapiens DNA mismatch repair protein Msh2 Proteins 0.000 description 1
- 101000909198 Homo sapiens DNA polymerase delta catalytic subunit Proteins 0.000 description 1
- 101001057603 Homo sapiens Dual specificity protein phosphatase 7 Proteins 0.000 description 1
- 101001045791 Homo sapiens High mobility group protein B2 Proteins 0.000 description 1
- 101000905054 Homo sapiens Histone H2A.Z Proteins 0.000 description 1
- 101001045116 Homo sapiens Homeobox protein Hox-A7 Proteins 0.000 description 1
- 101001006776 Homo sapiens Kinesin-like protein KIFC1 Proteins 0.000 description 1
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
- 101000687968 Homo sapiens Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase Proteins 0.000 description 1
- 101000603402 Homo sapiens Protein NPAT Proteins 0.000 description 1
- 101000770799 Homo sapiens Protein Wnt-10b Proteins 0.000 description 1
- 101001014035 Homo sapiens Protein p13 MTCP-1 Proteins 0.000 description 1
- 101000891649 Homo sapiens Transcription elongation factor A protein-like 1 Proteins 0.000 description 1
- 101000866336 Homo sapiens Transcription factor E2F5 Proteins 0.000 description 1
- 101001028730 Homo sapiens Transcription factor JunB Proteins 0.000 description 1
- 101000962461 Homo sapiens Transcription factor Maf Proteins 0.000 description 1
- 101000962469 Homo sapiens Transcription factor MafF Proteins 0.000 description 1
- 101000962473 Homo sapiens Transcription factor MafG Proteins 0.000 description 1
- 101000652707 Homo sapiens Transcription initiation factor TFIID subunit 4 Proteins 0.000 description 1
- 101000597045 Homo sapiens Transcriptional enhancer factor TEF-3 Proteins 0.000 description 1
- 101000836154 Homo sapiens Transforming acidic coiled-coil-containing protein 1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 102100036721 Insulin receptor Human genes 0.000 description 1
- 238000001265 Jonckheere trend test Methods 0.000 description 1
- 102100027942 Kinesin-like protein KIFC1 Human genes 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
- 101150002398 MCM5 gene Proteins 0.000 description 1
- 229910015837 MSH2 Inorganic materials 0.000 description 1
- 101150039798 MYC gene Proteins 0.000 description 1
- 102100024262 Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102000016397 Methyltransferase Human genes 0.000 description 1
- 101000596402 Mus musculus Neuronal vesicle trafficking-associated protein 1 Proteins 0.000 description 1
- 101001123364 Mus musculus Prolactin-2C3 Proteins 0.000 description 1
- 101100042796 Mus musculus Smc2 gene Proteins 0.000 description 1
- 101000800539 Mus musculus Translationally-controlled tumor protein Proteins 0.000 description 1
- 102100034670 Myb-related protein B Human genes 0.000 description 1
- 101710115153 Myb-related protein B Proteins 0.000 description 1
- 108010018525 NFATC Transcription Factors Proteins 0.000 description 1
- 102000002673 NFATC Transcription Factors Human genes 0.000 description 1
- 102100023904 Nuclear autoantigenic sperm protein Human genes 0.000 description 1
- 101710149564 Nuclear autoantigenic sperm protein Proteins 0.000 description 1
- 101710149892 Nucleoside diphosphate kinase B Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 1
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 208000008691 Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 102100025803 Progesterone receptor Human genes 0.000 description 1
- 102100038870 Protein NPAT Human genes 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 102100029062 Protein Wnt-10b Human genes 0.000 description 1
- 102100031352 Protein p13 MTCP-1 Human genes 0.000 description 1
- 101710150114 Protein rep Proteins 0.000 description 1
- 108010087776 Proto-Oncogene Proteins c-myb Proteins 0.000 description 1
- 102000009096 Proto-Oncogene Proteins c-myb Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 102100033982 Ran-binding protein 9 Human genes 0.000 description 1
- 101000613608 Rattus norvegicus Monocyte to macrophage differentiation factor Proteins 0.000 description 1
- 206010038111 Recurrent cancer Diseases 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 101710152114 Replication protein Proteins 0.000 description 1
- 108010034634 Repressor Proteins Proteins 0.000 description 1
- 102000009661 Repressor Proteins Human genes 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 101000781972 Schizosaccharomyces pombe (strain 972 / ATCC 24843) Protein wos2 Proteins 0.000 description 1
- 102100039024 Sphingosine kinase 1 Human genes 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 108700025695 Suppressor Genes Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 108050000808 TNF receptor-associated factor TRAF Proteins 0.000 description 1
- 102000008889 TNF receptor-associated factor TRAF Human genes 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Natural products O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 102100034838 Thymidine kinase, cytosolic Human genes 0.000 description 1
- 102000005497 Thymidylate Synthase Human genes 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
- 101001009610 Toxoplasma gondii Dense granule protein 5 Proteins 0.000 description 1
- 102100040250 Transcription elongation factor A protein-like 1 Human genes 0.000 description 1
- 102100031632 Transcription factor E2F5 Human genes 0.000 description 1
- 102100037168 Transcription factor JunB Human genes 0.000 description 1
- 102100039189 Transcription factor Maf Human genes 0.000 description 1
- 102100039187 Transcription factor MafF Human genes 0.000 description 1
- 102100039188 Transcription factor MafG Human genes 0.000 description 1
- 102100030833 Transcription initiation factor TFIID subunit 4 Human genes 0.000 description 1
- 102100035148 Transcriptional enhancer factor TEF-3 Human genes 0.000 description 1
- 102100027049 Transforming acidic coiled-coil-containing protein 1 Human genes 0.000 description 1
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 101100459258 Xenopus laevis myc-a gene Proteins 0.000 description 1
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 101150097482 ash2 gene Proteins 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 239000003719 aurora kinase inhibitor Substances 0.000 description 1
- 239000011324 bead Substances 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
- 210000000013 bile duct Anatomy 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004791 biological behavior Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000091 biomarker candidate Substances 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000012820 cell cycle checkpoint Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 230000003021 clonogenic effect Effects 0.000 description 1
- 210000004922 colonic epithelial cell Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 230000021953 cytokinesis Effects 0.000 description 1
- 230000002380 cytological effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000012774 diagnostic algorithm Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 230000005274 electronic transitions Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000003976 gap junction Anatomy 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 230000004547 gene signature Effects 0.000 description 1
- 210000001703 glandular epithelial cell Anatomy 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 108010027263 homeobox protein HOXA9 Proteins 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000006607 hypermethylation Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 208000020082 intraepithelial neoplasia Diseases 0.000 description 1
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 108010011989 karyopherin alpha 2 Proteins 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 239000000990 laser dye Substances 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000005004 lymphoid follicle Anatomy 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 238000011227 neoadjuvant chemotherapy Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- KPMKNHGAPDCYLP-UHFFFAOYSA-N nimustine hydrochloride Chemical compound Cl.CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 KPMKNHGAPDCYLP-UHFFFAOYSA-N 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 230000037443 ovarian carcinogenesis Effects 0.000 description 1
- 231100001249 ovarian carcinogenesis Toxicity 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 210000000277 pancreatic duct Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000014256 pre-replicative complex assembly Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000468 progesterone receptors Proteins 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000031267 regulation of DNA replication Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000037425 regulation of transcription Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 230000006335 response to radiation Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000009828 sister chromatid segregation Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 108010035597 sphingosine kinase Proteins 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 108010036901 thymidine kinase 1 Proteins 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 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
-
- 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
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/56—Staging of a disease; Further complications associated with the disease
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0720113.0A GB0720113D0 (en) | 2007-10-15 | 2007-10-15 | Diagnostic, prognostic and predictive testing for cancer |
| GB0720113.0 | 2007-10-15 | ||
| PCT/GB2008/003501 WO2009050461A1 (en) | 2007-10-15 | 2008-10-15 | Diagnostic, predictive and prognostic testing for cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2702653A1 true CA2702653A1 (en) | 2009-04-23 |
Family
ID=38813827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2702653A Abandoned CA2702653A1 (en) | 2007-10-15 | 2008-10-15 | Diagnostic, predictive and prognostic testing for cancer |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US8512716B2 (enExample) |
| EP (1) | EP2208070B1 (enExample) |
| JP (2) | JP5559056B2 (enExample) |
| CN (1) | CN101896819A (enExample) |
| AU (1) | AU2008313459B2 (enExample) |
| CA (1) | CA2702653A1 (enExample) |
| DK (1) | DK2208070T3 (enExample) |
| ES (1) | ES2395890T3 (enExample) |
| GB (1) | GB0720113D0 (enExample) |
| PT (1) | PT2208070E (enExample) |
| WO (1) | WO2009050461A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0921873D0 (en) | 2009-12-15 | 2010-01-27 | Cytosystems Ltd | Assay |
| SG10201505723UA (en) * | 2010-07-23 | 2015-09-29 | Harvard College | Methods for detecting signatures of disease or conditions in bodily fluids |
| AU2013388864B2 (en) * | 2013-05-09 | 2017-06-08 | The Procter & Gamble Company | Method and system for assessing health condition |
| CN103592444A (zh) * | 2013-11-27 | 2014-02-19 | 中国人民解放军沈阳军区总医院 | 一种检测乳腺癌中cyclin G1蛋白表达并进行预后评估的方法 |
| WO2015187498A1 (en) * | 2014-06-01 | 2015-12-10 | Novazoi Theranostics, Inc. | Compositions and methods for prognosis and treatment of neoplasm |
| WO2016131875A1 (en) * | 2015-02-17 | 2016-08-25 | Biontech Diagnostics Gmbh | Methods and kits for the molecular subtyping of bladder cancer |
| US11519916B2 (en) | 2015-06-08 | 2022-12-06 | Arquer Diagnostics Limited | Methods for analysing a urine sample |
| ES2911415T3 (es) | 2015-06-08 | 2022-05-19 | Arquer Diagnostics Ltd | Métodos y kits |
| CN105986034A (zh) * | 2016-06-15 | 2016-10-05 | 南京卡迪睿伯生物技术有限公司 | 一组胃癌基因的应用 |
| CN108344868B (zh) * | 2018-01-23 | 2020-05-15 | 郑州大学第一附属医院 | 人组蛋白H3 Ser10和Ser28在鉴定人早期胚胎的发育分期中的应用 |
| CN108344867B (zh) * | 2018-01-23 | 2020-05-15 | 郑州大学第一附属医院 | 人组蛋白H3 Ser10和Ser28在鉴定人卵母细胞成熟分期中的应用 |
| CN111187833A (zh) * | 2018-11-14 | 2020-05-22 | 上海生物芯片有限公司 | Plk1和bub1b基因联合作为肺癌生物标志物的用途 |
| GB201820867D0 (en) * | 2018-12-20 | 2019-02-06 | Arquer Diagnostics Ltd | Detection method |
| CN109988708B (zh) * | 2019-02-01 | 2022-12-09 | 碳逻辑生物科技(中山)有限公司 | 一种用于对患有结肠直肠癌的患者进行分型的系统 |
| CN110846413B (zh) * | 2019-11-23 | 2023-05-26 | 中南大学湘雅三医院 | Mafg/mafg-as1/mafg正反馈环作为靶位点检测试剂的应用 |
| CN114019163B (zh) * | 2021-11-02 | 2024-07-23 | 复旦大学附属中山医院 | 基于活化b细胞表达的结肠癌预后诊断用标记物及其用途 |
| WO2023150578A2 (en) * | 2022-02-01 | 2023-08-10 | 4D Path Inc. | Systems and methods for image-based disease characterization |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4329177A1 (de) * | 1993-08-30 | 1995-03-02 | Chemotherapeutisches Forschungsinstitut Georg Speyer Haus | Klonierung eines neuen Mitgliedes der Familie der Serin-Threonin-Kinasen |
| DE19915057A1 (de) | 1999-04-01 | 2000-10-19 | Forschungszentrum Borstel | Monoklonale Antikörper gegen das humane Mcm3 Protein, Verfahren zu ihrer Herstellung und ihre Verwendung |
| EP1422526A1 (en) | 2002-10-28 | 2004-05-26 | MTM Laboratories AG | Method for improved diagnosis of dysplasias |
| US20040231909A1 (en) * | 2003-01-15 | 2004-11-25 | Tai-Yang Luh | Motorized vehicle having forward and backward differential structure |
| GB0323225D0 (en) * | 2003-10-03 | 2003-11-05 | Ncc Technology Ventures Pte Lt | Materials and methods relating to breast cancer classification |
| DK2163650T3 (en) * | 2004-04-09 | 2015-11-02 | Genomic Health Inc | Genekspressionsmarkører for prediction of response to chemotherapy |
| EP1737982A4 (en) * | 2004-04-14 | 2009-09-23 | Harvard College | NUCLEIC ACID PROGRAMMABLE PROTEIN NETWORKS |
| US20060063190A1 (en) * | 2004-09-22 | 2006-03-23 | Tripath Imaging, Inc | Methods and compositions for evaluating breast cancer prognosis |
| WO2006087557A1 (en) * | 2005-02-18 | 2006-08-24 | Astrazeneca Ab | METHOD FOR DETERMINING RESPONSIVENESS TO CHKl INHIBITORS |
| DE602006011959D1 (de) * | 2005-12-30 | 2010-03-11 | Ventana Med Syst Inc | Na+, k+-atpase-expression bei zervixdysplasie und -krebs |
| EP1968579A1 (en) * | 2005-12-30 | 2008-09-17 | Astex Therapeutics Limited | Pharmaceutical compounds |
-
2007
- 2007-10-15 GB GBGB0720113.0A patent/GB0720113D0/en not_active Ceased
-
2008
- 2008-10-15 ES ES08840139T patent/ES2395890T3/es active Active
- 2008-10-15 JP JP2010529444A patent/JP5559056B2/ja not_active Expired - Fee Related
- 2008-10-15 PT PT88401393T patent/PT2208070E/pt unknown
- 2008-10-15 WO PCT/GB2008/003501 patent/WO2009050461A1/en not_active Ceased
- 2008-10-15 CN CN2008801209233A patent/CN101896819A/zh active Pending
- 2008-10-15 CA CA2702653A patent/CA2702653A1/en not_active Abandoned
- 2008-10-15 US US12/738,062 patent/US8512716B2/en not_active Expired - Fee Related
- 2008-10-15 AU AU2008313459A patent/AU2008313459B2/en not_active Ceased
- 2008-10-15 DK DK08840139.3T patent/DK2208070T3/da active
- 2008-10-15 EP EP08840139A patent/EP2208070B1/en not_active Not-in-force
-
2013
- 2013-04-30 US US13/873,487 patent/US20140154680A1/en not_active Abandoned
-
2014
- 2014-02-03 JP JP2014018906A patent/JP5837630B2/ja not_active Expired - Fee Related
-
2016
- 2016-04-29 US US15/141,908 patent/US20180223366A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014095726A (ja) | 2014-05-22 |
| GB0720113D0 (en) | 2007-11-28 |
| US20100285474A1 (en) | 2010-11-11 |
| AU2008313459A1 (en) | 2009-04-23 |
| US8512716B2 (en) | 2013-08-20 |
| DK2208070T3 (da) | 2012-12-17 |
| EP2208070A1 (en) | 2010-07-21 |
| CN101896819A (zh) | 2010-11-24 |
| JP5559056B2 (ja) | 2014-07-23 |
| JP2011501809A (ja) | 2011-01-13 |
| EP2208070B1 (en) | 2012-10-03 |
| WO2009050461A1 (en) | 2009-04-23 |
| JP5837630B2 (ja) | 2015-12-24 |
| PT2208070E (pt) | 2013-01-08 |
| US20140154680A1 (en) | 2014-06-05 |
| AU2008313459B2 (en) | 2013-01-24 |
| US20180223366A1 (en) | 2018-08-09 |
| ES2395890T3 (es) | 2013-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008313459B2 (en) | Diagnostic, predictive and prognostic testing for cancer | |
| Greene et al. | Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients | |
| Wangsa et al. | Near-tetraploid cancer cells show chromosome instability triggered by replication stress and exhibit enhanced invasiveness | |
| Heckl et al. | The ARID1A, p53 and ß-Catenin statuses are strong prognosticators in clear cell and endometrioid carcinoma of the ovary and the endometrium | |
| Ho et al. | Promoter methylation status of HIN-1 associated with outcomes of ovarian clear cell adenocarcinoma | |
| Banet et al. | HER-2 amplification in uterine serous carcinoma and serous endometrial intraepithelial carcinoma | |
| US20120245051A1 (en) | Objective, quantitative method to predict histological subtype in non-small cell lung cancer | |
| Barbolina et al. | Wilms tumor gene protein 1 is associated with ovarian cancer metastasis and modulates cell invasion | |
| Li et al. | Elevated expression of WSB2 degrades p53 and activates the IGFBP3-AKT-mTOR-dependent pathway to drive hepatocellular carcinoma | |
| Pierssens et al. | Chromosome instability in tumor resection margins of primary OSCC is a predictor of local recurrence | |
| Moreira et al. | Molecular characterization by immunocytochemistry of lung adenocarcinoma on cytology specimens | |
| Wu et al. | Combining the tyrosine kinase inhibitor cabozantinib and the mTORC1/2 inhibitor sapanisertib blocks ERK pathway activity and suppresses tumor growth in renal cell carcinoma | |
| Nolasco-Quiroga et al. | Increased expression of FAK isoforms as potential cancer biomarkers in ovarian cancer | |
| Heublein et al. | KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants | |
| US8071815B2 (en) | CTIP2 expression in squamous cell carcinoma | |
| Yakirevich et al. | Total Survivin and acetylated Survivin correlate with distinct molecular subtypes of breast cancer | |
| GB2519830A (en) | Methods for monitoring treatment response and relapse in ovarian cancer | |
| Davidson et al. | Different clinical roles for p21-activated kinase-1 in primary and recurrent ovarian carcinoma | |
| Liu et al. | Expression of p53, p16 and cyclooxygenase‐2 in esophageal cancer with tissue microarray | |
| CN117192123A (zh) | 一种评估鼻咽癌预后的生物标志物及其应用 | |
| US8609354B2 (en) | Method for selecting patients for treatment with an EGFR inhibitor | |
| CN102099493A (zh) | 用于预测对抗癌疗法的反应性的组合方法 | |
| Harb et al. | PYCR1, BANF1, and STARD8 Expression in Gastric Carcinoma: A Clinicopathologic, Prognostic, and Immunohistochemical Study | |
| Liu et al. | Targeting PIK3CB/YAP1 improves the sensitivity of paclitaxel by suppressing aging in head and neck squamous tumor cells | |
| WO2016133860A1 (en) | Cancer biomarkers and methods of use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20131015 |
|
| FZDE | Discontinued |
Effective date: 20190430 |