JP5559056B2 - ガンの診断、予測、および予後試験 - Google Patents
ガンの診断、予測、および予後試験 Download PDFInfo
- Publication number
- JP5559056B2 JP5559056B2 JP2010529444A JP2010529444A JP5559056B2 JP 5559056 B2 JP5559056 B2 JP 5559056B2 JP 2010529444 A JP2010529444 A JP 2010529444A JP 2010529444 A JP2010529444 A JP 2010529444A JP 5559056 B2 JP5559056 B2 JP 5559056B2
- Authority
- JP
- Japan
- Prior art keywords
- biomarker
- cancer
- level
- aurora
- cell cycle
- 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.)
- Expired - Fee Related
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 218
- 201000011510 cancer Diseases 0.000 title claims description 59
- 238000012360 testing method Methods 0.000 title description 17
- 238000003745 diagnosis Methods 0.000 title description 8
- 239000000090 biomarker Substances 0.000 claims description 193
- 230000022131 cell cycle Effects 0.000 claims description 113
- 102000004064 Geminin Human genes 0.000 claims description 92
- 108090000577 Geminin Proteins 0.000 claims description 92
- 238000000034 method Methods 0.000 claims description 71
- 101100533947 Mus musculus Serpina3k gene Proteins 0.000 claims description 53
- 101150070711 mcm2 gene Proteins 0.000 claims description 53
- 108010056274 polo-like kinase 1 Proteins 0.000 claims description 46
- 239000012472 biological sample Substances 0.000 claims description 40
- 206010006187 Breast cancer Diseases 0.000 claims description 35
- 208000026310 Breast neoplasm Diseases 0.000 claims description 35
- 238000004458 analytical method Methods 0.000 claims description 35
- 206010033128 Ovarian cancer Diseases 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 30
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 claims description 23
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 23
- 239000002246 antineoplastic agent Substances 0.000 claims description 13
- 238000001574 biopsy Methods 0.000 claims description 13
- 238000001514 detection method Methods 0.000 claims description 13
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 9
- 229940127089 cytotoxic agent Drugs 0.000 claims description 8
- 150000007523 nucleic acids Chemical group 0.000 claims description 7
- 238000002493 microarray Methods 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 6
- 238000003556 assay Methods 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 230000003321 amplification Effects 0.000 claims description 4
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 210000002700 urine Anatomy 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 238000010324 immunological assay Methods 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 238000003757 reverse transcription PCR Methods 0.000 claims description 3
- 238000002965 ELISA Methods 0.000 claims description 2
- 238000000636 Northern blotting Methods 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 238000002105 Southern blotting Methods 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 238000009595 pap smear Methods 0.000 claims description 2
- 210000003296 saliva Anatomy 0.000 claims description 2
- 238000007790 scraping Methods 0.000 claims description 2
- 210000002966 serum Anatomy 0.000 claims description 2
- 238000013518 transcription Methods 0.000 claims description 2
- 230000035897 transcription Effects 0.000 claims description 2
- 238000001262 western blot Methods 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000023915 Ureteral Neoplasms Diseases 0.000 claims 1
- 206010046392 Ureteric cancer Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 210000002200 mouth mucosa Anatomy 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 210000002381 plasma Anatomy 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 136
- 230000014509 gene expression Effects 0.000 description 77
- 230000004083 survival effect Effects 0.000 description 53
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 49
- 201000010099 disease Diseases 0.000 description 47
- 108090000623 proteins and genes Proteins 0.000 description 44
- 210000001519 tissue Anatomy 0.000 description 42
- -1 Ki67 Proteins 0.000 description 40
- 239000000523 sample Substances 0.000 description 34
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 33
- 230000002062 proliferating effect Effects 0.000 description 32
- 230000006369 cell cycle progression Effects 0.000 description 31
- 102000004169 proteins and genes Human genes 0.000 description 27
- 208000020584 Polyploidy Diseases 0.000 description 23
- 230000002159 abnormal effect Effects 0.000 description 23
- 230000000394 mitotic effect Effects 0.000 description 23
- 230000034614 regulation of DNA-dependent DNA replication initiation Effects 0.000 description 23
- 229920001184 polypeptide Polymers 0.000 description 22
- 102000004196 processed proteins & peptides Human genes 0.000 description 22
- 210000004881 tumor cell Anatomy 0.000 description 22
- 108020004414 DNA Proteins 0.000 description 19
- 102000001253 Protein Kinase Human genes 0.000 description 19
- 239000005441 aurora Substances 0.000 description 19
- 239000003814 drug Substances 0.000 description 19
- 239000003550 marker Substances 0.000 description 19
- 102000003989 Aurora kinases Human genes 0.000 description 17
- 108090000433 Aurora kinases Proteins 0.000 description 17
- 229940079593 drug Drugs 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
- 208000036878 aneuploidy Diseases 0.000 description 15
- 230000004069 differentiation Effects 0.000 description 15
- 238000004393 prognosis Methods 0.000 description 15
- 230000004044 response Effects 0.000 description 15
- 210000000481 breast Anatomy 0.000 description 14
- 230000010261 cell growth Effects 0.000 description 14
- 230000012010 growth Effects 0.000 description 14
- 230000035755 proliferation Effects 0.000 description 14
- 238000009509 drug development Methods 0.000 description 13
- 238000011527 multiparameter analysis Methods 0.000 description 13
- 108010033040 Histones Proteins 0.000 description 12
- 230000018199 S phase Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000002372 labelling Methods 0.000 description 12
- 230000011278 mitosis Effects 0.000 description 12
- 208000031448 Genomic Instability Diseases 0.000 description 11
- 230000003322 aneuploid effect Effects 0.000 description 11
- 238000009826 distribution Methods 0.000 description 11
- 230000007246 mechanism Effects 0.000 description 11
- 230000037361 pathway Effects 0.000 description 11
- 102000006947 Histones Human genes 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 239000011230 binding agent Substances 0.000 description 10
- 230000007704 transition Effects 0.000 description 10
- 230000001351 cycling effect Effects 0.000 description 9
- 230000008482 dysregulation Effects 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 9
- 230000004543 DNA replication Effects 0.000 description 8
- 206010058314 Dysplasia Diseases 0.000 description 8
- 101150029707 ERBB2 gene Proteins 0.000 description 8
- 230000004663 cell proliferation Effects 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 108050006400 Cyclin Proteins 0.000 description 7
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 7
- 102100038595 Estrogen receptor Human genes 0.000 description 7
- 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 7
- 210000001072 colon Anatomy 0.000 description 7
- 230000002596 correlated effect Effects 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 231100000517 death Toxicity 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 230000002018 overexpression Effects 0.000 description 7
- 230000027311 M phase Effects 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 6
- 239000008358 core component Substances 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 238000001325 log-rank test 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
- 102000020233 phosphotransferase Human genes 0.000 description 6
- 108060006633 protein kinase Proteins 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000010195 expression analysis Methods 0.000 description 5
- 238000003365 immunocytochemistry Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000003226 mitogen Substances 0.000 description 5
- 238000000491 multivariate analysis Methods 0.000 description 5
- 230000002611 ovarian Effects 0.000 description 5
- 210000001672 ovary Anatomy 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 230000000284 resting effect Effects 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 239000000758 substrate Substances 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
- 208000005623 Carcinogenesis Diseases 0.000 description 4
- 108010077544 Chromatin Proteins 0.000 description 4
- 102100037858 G1/S-specific cyclin-E1 Human genes 0.000 description 4
- 101000738568 Homo sapiens G1/S-specific cyclin-E1 Proteins 0.000 description 4
- 101150023098 Mcm7 gene 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
- 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
- 231100001075 aneuploidy Toxicity 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000036952 cancer formation Effects 0.000 description 4
- 231100000504 carcinogenesis Toxicity 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 210000003483 chromatin Anatomy 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 239000000306 component Substances 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 230000003828 downregulation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 238000003119 immunoblot 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
- 230000007170 pathology Effects 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
- 239000012130 whole-cell lysate Substances 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
- 102000016559 DNA Primase Human genes 0.000 description 3
- 108010092681 DNA Primase Proteins 0.000 description 3
- 102000003915 DNA Topoisomerases Human genes 0.000 description 3
- 108090000323 DNA Topoisomerases Proteins 0.000 description 3
- 230000010190 G1 phase Effects 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
- 101150002398 MCM5 gene Proteins 0.000 description 3
- 101150004492 Mcm3 gene Proteins 0.000 description 3
- 101150088918 Mcm6 gene Proteins 0.000 description 3
- 206010061309 Neoplasm progression Diseases 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
- 238000011226 adjuvant chemotherapy Methods 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 208000035269 cancer or benign tumor Diseases 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
- 239000003795 chemical substances by application Substances 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 210000003238 esophagus Anatomy 0.000 description 3
- 229960005420 etoposide Drugs 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
- 238000000684 flow cytometry Methods 0.000 description 3
- 238000012744 immunostaining Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 230000000306 recurrent effect Effects 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
- 229940126585 therapeutic drug Drugs 0.000 description 3
- 230000005751 tumor progression Effects 0.000 description 3
- 238000007473 univariate analysis Methods 0.000 description 3
- 238000011144 upstream manufacturing 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
- 108010060385 Cyclin B1 Proteins 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
- 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
- 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
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 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
- 108010087740 Fanconi Anemia Complementation Group A protein Proteins 0.000 description 2
- 102000009095 Fanconi Anemia Complementation Group A protein Human genes 0.000 description 2
- 201000000106 Fanconi anemia complementation group A Diseases 0.000 description 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
- 102100032340 G2/mitotic-specific cyclin-B1 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
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 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
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 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
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases 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
- 102100030086 Receptor tyrosine-protein kinase erbB-2 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
- 102000000505 Ribonucleotide Reductases Human genes 0.000 description 2
- 108010041388 Ribonucleotide Reductases Proteins 0.000 description 2
- 238000003646 Spearman's rank correlation coefficient Methods 0.000 description 2
- 102100037616 Spermine synthase Human genes 0.000 description 2
- 108010071698 Spermine synthase Proteins 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
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 2
- 102000001742 Tumor Suppressor Proteins Human genes 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
- 230000005856 abnormality Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000035508 accumulation Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000006978 adaptation Effects 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
- 238000004166 bioassay Methods 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
- 239000010839 body fluid Substances 0.000 description 2
- 230000023359 cell cycle switching, meiotic to mitotic cell cycle Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000003793 centrosome Anatomy 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 230000002380 cytological effect Effects 0.000 description 2
- 238000004163 cytometry Methods 0.000 description 2
- 238000012303 cytoplasmic staining Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 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
- 208000035475 disorder Diseases 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 238000005538 encapsulation Methods 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
- 229940088598 enzyme Drugs 0.000 description 2
- 229960001904 epirubicin Drugs 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000007850 fluorescent dye 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
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000005764 inhibitory process Effects 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
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000000463 material Substances 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
- 210000000214 mouth Anatomy 0.000 description 2
- 210000005170 neoplastic cell Anatomy 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 239000012188 paraffin wax Substances 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
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 230000009467 reduction 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
- 230000008093 supporting effect Effects 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000004797 therapeutic response Effects 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
- 229940035893 uracil Drugs 0.000 description 2
- 210000003932 urinary bladder Anatomy 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
- LNXQPKVVMPYAJM-UHFFFAOYSA-N 1-(4-amino-2-methylpyrimidin-5-yl)-3-(2-chloroethyl)-1-methyl-3-nitrosourea hydrochloride Chemical compound Cl.ClCCN(N=O)C(=O)N(C)C1=CN=C(C)N=C1N LNXQPKVVMPYAJM-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
- 101000783817 Agaricus bisporus lectin Proteins 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
- 208000004736 B-Cell Leukemia Diseases 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
- 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
- 102100024506 Bone morphogenetic protein 2 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
- 108091060290 Chromatid Proteins 0.000 description 1
- 102100038602 Chromatin assembly factor 1 subunit A 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
- 102000010970 Connexin Human genes 0.000 description 1
- 108050001175 Connexin Proteins 0.000 description 1
- 229920000742 Cotton Polymers 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
- 108010058546 Cyclin D1 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
- 108010016788 Cyclin-Dependent Kinase Inhibitor p21 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
- 102100033270 Cyclin-dependent kinase inhibitor 1 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
- 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
- 230000006820 DNA synthesis Effects 0.000 description 1
- 229940124087 DNA topoisomerase II inhibitor Drugs 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
- 101100239628 Danio rerio myca gene Proteins 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 101100216227 Dictyostelium discoideum anapc3 gene Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 101710155964 Diuretic hormone 1 Proteins 0.000 description 1
- 101001084710 Drosophila melanogaster Histone H2A.v Proteins 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
- 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
- 102100024165 G1/S-specific cyclin-D1 Human genes 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
- 206010064571 Gene mutation Diseases 0.000 description 1
- 101150018826 Gja6 gene Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 208000002250 Hematologic Neoplasms 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
- 101000741348 Homo sapiens Chromatin assembly factor 1 subunit A 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
- 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
- 101000588130 Homo sapiens Microsomal triglyceride transfer protein large subunit 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
- 101001092125 Homo sapiens Replication protein A 70 kDa DNA-binding subunit 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
- 101000823316 Homo sapiens Tyrosine-protein kinase ABL1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 102100036721 Insulin receptor Human genes 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
- 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
- 241001465754 Metazoa Species 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
- 108700020796 Oncogene Proteins 0.000 description 1
- 108010067244 Origin Recognition Complex Proteins 0.000 description 1
- 102100040591 Origin recognition complex subunit 1 Human genes 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 101150046160 POL1 gene 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
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 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
- 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
- 102100025803 Progesterone receptor Human genes 0.000 description 1
- 108091008611 Protein Kinase B Proteins 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
- 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
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 102100035729 Replication protein A 70 kDa DNA-binding subunit 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
- 229940123237 Taxane Drugs 0.000 description 1
- 101100117436 Thermus aquaticus polA gene Proteins 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
- 101710183280 Topoisomerase Proteins 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
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 102100027049 Transforming acidic coiled-coil-containing protein 1 Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes 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 group C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 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
- 230000004791 biological behavior Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 230000007321 biological mechanism 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
- 210000000069 breast epithelial cell Anatomy 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000007444 cell Immobilization Methods 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000012820 cell cycle checkpoint Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 210000004756 chromatid Anatomy 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 230000003021 clonogenic effect Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 238000012774 diagnostic algorithm Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000002222 downregulating effect Effects 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
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 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
- 229960000961 floxuridine Drugs 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
- 239000012634 fragment Substances 0.000 description 1
- 208000028270 functioning endocrine neoplasm Diseases 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000003976 gap junction Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 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
- 229960005277 gemcitabine Drugs 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
- 210000003494 hepatocyte Anatomy 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
- 108091006086 inhibitor proteins Proteins 0.000 description 1
- 230000009545 invasion Effects 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
- 239000000990 laser dye Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 230000003211 malignant 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
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002547 new drug Substances 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
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000006508 oncogene activation Effects 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 102000027450 oncoproteins Human genes 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
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000002980 postoperative effect 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
- 238000002203 pretreatment Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 108090000468 progesterone receptors Proteins 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 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
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 230000006335 response to radiation 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
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid 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
- 238000003860 storage Methods 0.000 description 1
- 239000012536 storage buffer Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 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
- 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
- 230000000699 topical effect Effects 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
- 230000005740 tumor formation Effects 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 238000011870 unpaired t-test Methods 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
Images
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 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014018906A Division JP5837630B2 (ja) | 2007-10-15 | 2014-02-03 | ガンの診断、予測、および予後試験 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011501809A JP2011501809A (ja) | 2011-01-13 |
| JP5559056B2 true JP5559056B2 (ja) | 2014-07-23 |
Family
ID=38813827
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010529444A Expired - Fee Related JP5559056B2 (ja) | 2007-10-15 | 2008-10-15 | ガンの診断、予測、および予後試験 |
| JP2014018906A Expired - Fee Related JP5837630B2 (ja) | 2007-10-15 | 2014-02-03 | ガンの診断、予測、および予後試験 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014018906A Expired - Fee Related JP5837630B2 (ja) | 2007-10-15 | 2014-02-03 | ガンの診断、予測、および予後試験 |
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 |
| CA2702653A1 (en) | 2009-04-23 |
| 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 |
| 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 |
|---|---|---|
| JP5837630B2 (ja) | ガンの診断、予測、および予後試験 | |
| Ho et al. | Promoter methylation status of HIN-1 associated with outcomes of ovarian clear cell adenocarcinoma | |
| WO2012024612A1 (en) | Cancer diagnostic and cancer therapeutic | |
| US20100081666A1 (en) | Src activation for determining cancer prognosis and as a target for cancer therapy | |
| US20120245051A1 (en) | Objective, quantitative method to predict histological subtype in non-small cell lung cancer | |
| WO2022053065A1 (zh) | 用于预测或评估肺癌患者的生物标志物、检测方法及应用 | |
| Li et al. | Elevated expression of WSB2 degrades p53 and activates the IGFBP3-AKT-mTOR-dependent pathway to drive hepatocellular carcinoma | |
| Yang et al. | HMGA1 promotes hepatic metastasis of colorectal cancer by inducing expression of glucose transporter 3 (GLUT3) | |
| Chen et al. | The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma | |
| US20240084400A1 (en) | Methods for prognosing, diagnosing, and treating colorectal cancer | |
| Li et al. | Overexpression of MEF2D contributes to oncogenic malignancy and chemotherapeutic resistance in ovarian carcinoma | |
| US20140186837A1 (en) | Methods For Diagnosing Cancer | |
| JP2017508147A (ja) | ステージｉｉの結腸直腸がんにおける予測マーカーとしてのｇアルファ相互作用小胞結合タンパク質（ｇｉｖ） | |
| Li et al. | RETRACTED ARTICLE: Octamer transcription factor 1 mediates epithelial-mesenchymal transition in colorectal cancer | |
| GB2519830A (en) | Methods for monitoring treatment response and relapse in ovarian cancer | |
| Evans et al. | Microarray and RNA in situ hybridization assay for recurrence risk markers of breast carcinoma and ductal carcinoma in situ: Evidence supporting the use of diverse pathways panels | |
| Hunt et al. | Extensive intratumor proteogenomic heterogeneity revealed by multiregion sampling in high-grade serous Ovarian tumor specimens | |
| EP2574929A1 (en) | Marker in diagnosing prostate cancer (PC) | |
| Mamat@ Yusof et al. | Gene expression and soluble protein level of PD-1 and its ligands (PD-L1 and PD-L2) in endometrial cancer | |
| JP2017529074A (ja) | 治療剤に対する抵抗性の診断に使用するためのＥＲＣＣ１アイソフォーム３のｍＲＮＡおよび／またはタンパク質ならびにこのｍＲＮＡおよび／またはタンパク質を使用する治療剤に対する抵抗性を診断するための方法 | |
| US11360094B2 (en) | Method for measuring MRE11 in tissues to predict cystectomy or bladder sparing surgery plus chemoradiation therapy | |
| Rabien et al. | Cancer Treated by Adjuvant Chemotherapy | |
| EP2236625A1 (en) | Use of trefoil factor family 3 (tff3) in the prognosis of patients diagnosed with colorectal cancer | |
| Scerri | Herceptin® resistance in breast cancer: a pathwaybased approach | |
| Giovanni Mellilo et al. | prognostic factor in ovarian carcinoma |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20120104 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120403 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120702 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120911 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121210 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20131001 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140203 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20140411 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140507 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140605 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5559056 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |