JP2006510363A - 癌およびその前駆病変の検出のための化合物および方法 - Google Patents
癌およびその前駆病変の検出のための化合物および方法 Download PDFInfo
- Publication number
- JP2006510363A JP2006510363A JP2004560521A JP2004560521A JP2006510363A JP 2006510363 A JP2006510363 A JP 2006510363A JP 2004560521 A JP2004560521 A JP 2004560521A JP 2004560521 A JP2004560521 A JP 2004560521A JP 2006510363 A JP2006510363 A JP 2006510363A
- Authority
- JP
- Japan
- Prior art keywords
- dnase
- cancer
- polypeptide
- detection
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 273
- 238000001514 detection method Methods 0.000 title claims abstract description 149
- 150000001875 compounds Chemical class 0.000 title claims abstract description 82
- 230000003902 lesion Effects 0.000 title claims abstract description 67
- 239000002243 precursor Substances 0.000 title claims abstract description 57
- 206010028980 Neoplasm Diseases 0.000 title claims description 148
- 201000011510 cancer Diseases 0.000 title claims description 69
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 354
- 108010053770 Deoxyribonucleases Proteins 0.000 claims abstract description 316
- 102000016911 Deoxyribonucleases Human genes 0.000 claims abstract description 309
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 291
- 229920001184 polypeptide Polymers 0.000 claims abstract description 252
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 150
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 139
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 139
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 62
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 201000010099 disease Diseases 0.000 claims abstract description 33
- 238000004393 prognosis Methods 0.000 claims abstract description 10
- 238000013399 early diagnosis Methods 0.000 claims abstract description 3
- 230000004960 subcellular localization Effects 0.000 claims abstract description 3
- 210000004027 cell Anatomy 0.000 claims description 141
- 239000000523 sample Substances 0.000 claims description 115
- 230000014509 gene expression Effects 0.000 claims description 63
- 210000001519 tissue Anatomy 0.000 claims description 61
- 101710094552 Deoxyribonuclease-1-like 1 Proteins 0.000 claims description 60
- 102100022872 Deoxyribonuclease-1-like 1 Human genes 0.000 claims description 60
- 238000006243 chemical reaction Methods 0.000 claims description 58
- 230000000694 effects Effects 0.000 claims description 56
- 239000003550 marker Substances 0.000 claims description 56
- 238000009739 binding Methods 0.000 claims description 47
- 230000027455 binding Effects 0.000 claims description 45
- 239000012634 fragment Substances 0.000 claims description 43
- 239000000427 antigen Substances 0.000 claims description 42
- 108091007433 antigens Proteins 0.000 claims description 42
- 102000036639 antigens Human genes 0.000 claims description 42
- 238000012360 testing method Methods 0.000 claims description 39
- 239000000126 substance Substances 0.000 claims description 29
- 208000035475 disorder Diseases 0.000 claims description 28
- 230000003321 amplification Effects 0.000 claims description 25
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 22
- 239000003112 inhibitor Substances 0.000 claims description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims description 18
- 238000003745 diagnosis Methods 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 239000012190 activator Substances 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 15
- 238000003384 imaging method Methods 0.000 claims description 14
- 238000000338 in vitro Methods 0.000 claims description 14
- 238000012216 screening Methods 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 13
- 238000011065 in-situ storage Methods 0.000 claims description 13
- 206010009944 Colon cancer Diseases 0.000 claims description 12
- 102000004190 Enzymes Human genes 0.000 claims description 11
- 108090000790 Enzymes Proteins 0.000 claims description 11
- 210000001124 body fluid Anatomy 0.000 claims description 11
- 239000010839 body fluid Substances 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 238000001727 in vivo Methods 0.000 claims description 11
- 239000012530 fluid Substances 0.000 claims description 10
- 210000002966 serum Anatomy 0.000 claims description 10
- 239000005557 antagonist Substances 0.000 claims description 9
- 239000000872 buffer Substances 0.000 claims description 9
- 210000002700 urine Anatomy 0.000 claims description 9
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 239000000556 agonist Substances 0.000 claims description 8
- 229940000406 drug candidate Drugs 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 230000004044 response Effects 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 230000004663 cell proliferation Effects 0.000 claims description 7
- 238000011160 research Methods 0.000 claims description 7
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 6
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 6
- 230000024245 cell differentiation Effects 0.000 claims description 6
- 201000010881 cervical cancer Diseases 0.000 claims description 6
- 201000005202 lung cancer Diseases 0.000 claims description 6
- 208000020816 lung neoplasm Diseases 0.000 claims description 6
- 230000028327 secretion Effects 0.000 claims description 6
- 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 claims description 5
- 210000001185 bone marrow Anatomy 0.000 claims description 5
- 230000008859 change Effects 0.000 claims description 5
- 210000004392 genitalia Anatomy 0.000 claims description 5
- 210000004698 lymphocyte Anatomy 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 4
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 4
- 238000001574 biopsy Methods 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 230000009870 specific binding Effects 0.000 claims description 4
- 238000009007 Diagnostic Kit Methods 0.000 claims description 3
- 229960002685 biotin Drugs 0.000 claims description 3
- 235000020958 biotin Nutrition 0.000 claims description 3
- 239000011616 biotin Substances 0.000 claims description 3
- 210000000416 exudates and transudate Anatomy 0.000 claims description 3
- 201000005787 hematologic cancer Diseases 0.000 claims description 3
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 3
- 210000003296 saliva Anatomy 0.000 claims description 3
- 210000000582 semen Anatomy 0.000 claims description 3
- 230000002485 urinary effect Effects 0.000 claims description 3
- 102100038023 DNA fragmentation factor subunit beta Human genes 0.000 claims description 2
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 claims description 2
- 101000891568 Homo sapiens Putative deoxyribonuclease TATDN2 Proteins 0.000 claims description 2
- 102100040260 Putative deoxyribonuclease TATDN2 Human genes 0.000 claims description 2
- 239000007853 buffer solution Substances 0.000 claims description 2
- 108010042238 caspase-activated deoxyribonuclease Proteins 0.000 claims description 2
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 claims description 2
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 claims description 2
- 108010035817 human DNA fragmentation factor Proteins 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 210000002751 lymph Anatomy 0.000 claims description 2
- 210000002381 plasma Anatomy 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims 2
- 201000010536 head and neck cancer Diseases 0.000 claims 2
- 208000029559 malignant endocrine neoplasm Diseases 0.000 claims 2
- 210000000578 peripheral nerve Anatomy 0.000 claims 2
- 230000000241 respiratory effect Effects 0.000 claims 2
- 210000004872 soft tissue Anatomy 0.000 claims 2
- 208000006593 Urologic Neoplasms Diseases 0.000 claims 1
- 102000008277 human DNA fragmentation factor Human genes 0.000 claims 1
- 238000012123 point-of-care testing Methods 0.000 claims 1
- 201000009030 Carcinoma Diseases 0.000 abstract description 31
- 239000012472 biological sample Substances 0.000 abstract description 12
- 238000012544 monitoring process Methods 0.000 abstract description 10
- 108090000623 proteins and genes Proteins 0.000 description 100
- 102000004169 proteins and genes Human genes 0.000 description 87
- 235000018102 proteins Nutrition 0.000 description 81
- 238000010186 staining Methods 0.000 description 54
- 239000011230 binding agent Substances 0.000 description 37
- 238000004458 analytical method Methods 0.000 description 33
- 230000002163 immunogen Effects 0.000 description 27
- 241001465754 Metazoa Species 0.000 description 24
- 210000001744 T-lymphocyte Anatomy 0.000 description 23
- 102000040430 polynucleotide Human genes 0.000 description 23
- 108091033319 polynucleotide Proteins 0.000 description 23
- 239000002157 polynucleotide Substances 0.000 description 23
- 238000000926 separation method Methods 0.000 description 22
- 238000002360 preparation method Methods 0.000 description 21
- 210000004881 tumor cell Anatomy 0.000 description 20
- 239000013598 vector Substances 0.000 description 19
- 230000001900 immune effect Effects 0.000 description 18
- 230000009261 transgenic effect Effects 0.000 description 18
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 230000001105 regulatory effect Effects 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 16
- 108020003175 receptors Proteins 0.000 description 16
- 125000005647 linker group Chemical group 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 230000002159 abnormal effect Effects 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000009169 immunotherapy Methods 0.000 description 14
- 150000001413 amino acids Chemical class 0.000 description 13
- 230000000984 immunochemical effect Effects 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 239000002671 adjuvant Substances 0.000 description 12
- 108091023040 Transcription factor Proteins 0.000 description 11
- -1 antibodies Substances 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 230000004071 biological effect Effects 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 10
- 102000004127 Cytokines Human genes 0.000 description 10
- 230000000692 anti-sense effect Effects 0.000 description 10
- 230000002380 cytological effect Effects 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- 108020004999 messenger RNA Proteins 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 230000002018 overexpression Effects 0.000 description 10
- 230000002062 proliferating effect Effects 0.000 description 10
- 238000013518 transcription Methods 0.000 description 10
- 230000035897 transcription Effects 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- 206010027476 Metastases Diseases 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 230000010261 cell growth Effects 0.000 description 9
- 230000012010 growth Effects 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 238000004949 mass spectrometry Methods 0.000 description 9
- 239000002773 nucleotide Substances 0.000 description 9
- 125000003729 nucleotide group Chemical group 0.000 description 9
- 239000007790 solid phase Substances 0.000 description 9
- 238000002255 vaccination Methods 0.000 description 9
- 108091005461 Nucleic proteins Proteins 0.000 description 8
- 238000013461 design Methods 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 239000000975 dye Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 239000000816 peptidomimetic Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 108090000994 Catalytic RNA Proteins 0.000 description 7
- 102000053642 Catalytic RNA Human genes 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 206010036790 Productive cough Diseases 0.000 description 7
- 230000000890 antigenic effect Effects 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 206010017758 gastric cancer Diseases 0.000 description 7
- 210000001035 gastrointestinal tract Anatomy 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 108091092562 ribozyme Proteins 0.000 description 7
- 210000003802 sputum Anatomy 0.000 description 7
- 208000024794 sputum Diseases 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 210000004379 membrane Anatomy 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 208000005718 Stomach Neoplasms Diseases 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 210000000481 breast Anatomy 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 210000000805 cytoplasm Anatomy 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 230000001613 neoplastic effect Effects 0.000 description 5
- 239000011148 porous material Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 206010038038 rectal cancer Diseases 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 201000011549 stomach cancer Diseases 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 229960005486 vaccine Drugs 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 108050006400 Cyclin Proteins 0.000 description 4
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 4
- 208000006402 Ductal Carcinoma Diseases 0.000 description 4
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 238000002405 diagnostic procedure Methods 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000012760 immunocytochemical staining Methods 0.000 description 4
- 238000011532 immunohistochemical staining Methods 0.000 description 4
- 238000001114 immunoprecipitation Methods 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 229920002521 macromolecule Polymers 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 239000004005 microsphere Substances 0.000 description 4
- 230000003278 mimic effect Effects 0.000 description 4
- 238000012758 nuclear staining Methods 0.000 description 4
- 239000002853 nucleic acid probe Substances 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 150000002894 organic compounds Chemical class 0.000 description 4
- 229920002401 polyacrylamide Polymers 0.000 description 4
- 229920001282 polysaccharide Polymers 0.000 description 4
- 239000005017 polysaccharide Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 230000008467 tissue growth Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108020005544 Antisense RNA Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 206010048832 Colon adenoma Diseases 0.000 description 3
- 229920000742 Cotton Polymers 0.000 description 3
- 102000016736 Cyclin Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108010038807 Oligopeptides Proteins 0.000 description 3
- 102000015636 Oligopeptides Human genes 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 108010067902 Peptide Library Proteins 0.000 description 3
- 208000015634 Rectal Neoplasms Diseases 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 208000009956 adenocarcinoma Diseases 0.000 description 3
- 238000001042 affinity chromatography Methods 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 201000010897 colon adenocarcinoma Diseases 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000002052 colonoscopy Methods 0.000 description 3
- 239000003184 complementary RNA Substances 0.000 description 3
- 238000004590 computer program Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000005206 flow analysis Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000002649 immunization Methods 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000002055 immunohistochemical effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000011221 initial treatment Methods 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 150000002611 lead compounds Chemical class 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 230000011987 methylation Effects 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 238000000053 physical method Methods 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 210000001236 prokaryotic cell Anatomy 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000002797 proteolythic effect Effects 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 201000001275 rectum cancer Diseases 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000012588 trypsin Substances 0.000 description 3
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 3
- 230000005951 type IV hypersensitivity Effects 0.000 description 3
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 3
- NJNAHFYVTBZQHU-LFFUDGMSSA-N (2s,5s,6r,10r,11s)-5-benzyl-10-heptyl-6-hydroxy-4,11-dimethyl-2-propan-2-yl-1,9-dioxa-4-azacyclododecane-3,8,12-trione Chemical compound CN1C(=O)[C@H](C(C)C)OC(=O)[C@@H](C)[C@@H](CCCCCCC)OC(=O)C[C@@H](O)[C@@H]1CC1=CC=CC=C1 NJNAHFYVTBZQHU-LFFUDGMSSA-N 0.000 description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
- 206010061424 Anal cancer Diseases 0.000 description 2
- 208000007860 Anus Neoplasms Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 108091007914 CDKs Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 2
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- 238000011510 Elispot assay Methods 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 102100039556 Galectin-4 Human genes 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 206010073069 Hepatic cancer Diseases 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 206010023774 Large cell lung cancer Diseases 0.000 description 2
- 208000032271 Malignant tumor of penis Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 206010027406 Mesothelioma Diseases 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 206010027457 Metastases to liver Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010033733 Papule Diseases 0.000 description 2
- 208000002471 Penile Neoplasms Diseases 0.000 description 2
- 206010034299 Penile cancer Diseases 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 238000010847 SEQUEST Methods 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 206010047741 Vulval cancer Diseases 0.000 description 2
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 201000011165 anus cancer Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 201000001531 bladder carcinoma Diseases 0.000 description 2
- 238000013276 bronchoscopy Methods 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 238000005251 capillar electrophoresis Methods 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 238000005341 cation exchange Methods 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 201000003565 cervix uteri carcinoma in situ Diseases 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 201000010989 colorectal carcinoma Diseases 0.000 description 2
- 208000028231 connective and soft tissue neoplasm Diseases 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 2
- 238000002784 cytotoxicity assay Methods 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 210000003890 endocrine cell Anatomy 0.000 description 2
- 201000011523 endocrine gland cancer Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 208000010749 gastric carcinoma Diseases 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- NJNAHFYVTBZQHU-UHFFFAOYSA-N hapalosin Natural products CN1C(=O)C(C(C)C)OC(=O)C(C)C(CCCCCCC)OC(=O)CC(O)C1CC1=CC=CC=C1 NJNAHFYVTBZQHU-UHFFFAOYSA-N 0.000 description 2
- 108010048227 hapalosin Proteins 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 230000002390 hyperplastic effect Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000011503 in vivo imaging Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 230000009878 intermolecular interaction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000008863 intramolecular interaction Effects 0.000 description 2
- 238000005040 ion trap Methods 0.000 description 2
- 239000004816 latex Substances 0.000 description 2
- 229920000126 latex Polymers 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 201000002250 liver carcinoma Diseases 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- 201000009546 lung large cell carcinoma Diseases 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 230000009826 neoplastic cell growth Effects 0.000 description 2
- 210000002445 nipple Anatomy 0.000 description 2
- 238000000399 optical microscopy Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 238000011197 physicochemical method Methods 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 208000020615 rectal carcinoma Diseases 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000009703 regulation of cell differentiation Effects 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 208000022159 squamous carcinoma in situ Diseases 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 201000000498 stomach carcinoma Diseases 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 238000010396 two-hybrid screening Methods 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 2
- 208000022625 uterine cervix carcinoma in situ Diseases 0.000 description 2
- 210000001215 vagina Anatomy 0.000 description 2
- 206010046885 vaginal cancer Diseases 0.000 description 2
- 208000013139 vaginal neoplasm Diseases 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 201000005102 vulva cancer Diseases 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- PVPBBTJXIKFICP-UHFFFAOYSA-N (7-aminophenothiazin-3-ylidene)azanium;chloride Chemical compound [Cl-].C1=CC(=[NH2+])C=C2SC3=CC(N)=CC=C3N=C21 PVPBBTJXIKFICP-UHFFFAOYSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- 238000004780 2D liquid chromatography Methods 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- JYLNVJYYQQXNEK-UHFFFAOYSA-N 3-amino-2-(4-chlorophenyl)-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(CN)C1=CC=C(Cl)C=C1 JYLNVJYYQQXNEK-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 102100036464 Activated RNA polymerase II transcriptional coactivator p15 Human genes 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101150002728 CDC6 gene Proteins 0.000 description 1
- 101150012716 CDK1 gene Proteins 0.000 description 1
- 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 102000005483 Cell Cycle Proteins Human genes 0.000 description 1
- 108010031896 Cell Cycle Proteins Proteins 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008263 Cervical dysplasia Diseases 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 108010068192 Cyclin A Proteins 0.000 description 1
- 102000002554 Cyclin A Human genes 0.000 description 1
- 102000003909 Cyclin E Human genes 0.000 description 1
- 108090000257 Cyclin E Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108010071146 DNA Polymerase III Proteins 0.000 description 1
- 102000007528 DNA Polymerase III Human genes 0.000 description 1
- 102100038026 DNA fragmentation factor subunit alpha Human genes 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 1
- 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 238000002738 Giemsa staining Methods 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 1
- 101000902865 Homo sapiens Deoxyribonuclease-1-like 1 Proteins 0.000 description 1
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 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 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 101150002398 MCM5 gene Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101150088918 Mcm6 gene Proteins 0.000 description 1
- 101150023098 Mcm7 gene Proteins 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108010038988 Peptide Hormones Proteins 0.000 description 1
- 102000015731 Peptide Hormones Human genes 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 101710182846 Polyhedrin Proteins 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710149951 Protein Tat Proteins 0.000 description 1
- 102100028588 Protein ZNRD2 Human genes 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 102100022151 Ragulator complex protein LAMTOR1 Human genes 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 206010029107 Respiratory Tract Neoplasms Diseases 0.000 description 1
- 102100038042 Retinoblastoma-associated protein Human genes 0.000 description 1
- 101710124357 Retinoblastoma-associated protein Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010079723 Shiga Toxin Proteins 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000062793 Sorghum vulgare Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000033781 Thyroid carcinoma Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102100040250 Transcription elongation factor A protein-like 1 Human genes 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 108010079351 Tumor Suppressor Protein p14ARF Proteins 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003171 anti-complementary effect Effects 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 239000012122 aqueous mounting media Substances 0.000 description 1
- 210000001815 ascending colon Anatomy 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical compound [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 101150073031 cdk2 gene Proteins 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 208000025997 central nervous system neoplasm Diseases 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- JBTHDAVBDKKSRW-UHFFFAOYSA-N chembl1552233 Chemical compound CC1=CC(C)=CC=C1N=NC1=C(O)C=CC2=CC=CC=C12 JBTHDAVBDKKSRW-UHFFFAOYSA-N 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- ZYVSOIYQKUDENJ-WKSBCEQHSA-N chromomycin A3 Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@@H]1OC(C)=O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](O[C@@H]3O[C@@H](C)[C@H](OC(C)=O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@@H]1C[C@@H](O)[C@@H](OC)[C@@H](C)O1 ZYVSOIYQKUDENJ-WKSBCEQHSA-N 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 201000002758 colorectal adenoma Diseases 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 238000011960 computer-aided design Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
- 230000000093 cytochemical effect Effects 0.000 description 1
- 238000012303 cytoplasmic staining Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- WHHGLZMJPXIBIX-UHFFFAOYSA-N decabromodiphenyl ether Chemical compound BrC1=C(Br)C(Br)=C(Br)C(Br)=C1OC1=C(Br)C(Br)=C(Br)C(Br)=C1Br WHHGLZMJPXIBIX-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 210000001731 descending colon Anatomy 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000002101 electrospray ionisation tandem mass spectrometry Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 210000003372 endocrine gland Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 210000003236 esophagogastric junction Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000001997 free-flow electrophoresis Methods 0.000 description 1
- 231100001014 gastrointestinal tract lesion Toxicity 0.000 description 1
- 238000002575 gastroscopy Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229940116886 human interleukin-6 Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000009607 mammography Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 101150061358 mcm-4 gene Proteins 0.000 description 1
- 101150070711 mcm2 gene Proteins 0.000 description 1
- 101150024228 mdm2 gene Proteins 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960000901 mepacrine Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000019713 millet Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000001821 nucleic acid purification Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000009595 pap smear Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 201000005528 peripheral nervous system neoplasm Diseases 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000004633 phorbol derivatives Chemical class 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- 238000000206 photolithography Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 108700028325 pokeweed antiviral Proteins 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- GPKJTRJOBQGKQK-UHFFFAOYSA-N quinacrine Chemical compound C1=C(OC)C=C2C(NC(C)CCCN(CC)CC)=C(C=CC(Cl)=C3)C3=NC2=C1 GPKJTRJOBQGKQK-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000012385 regulation of binding Effects 0.000 description 1
- 230000021014 regulation of cell growth Effects 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000001599 sigmoid colon Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 238000012799 strong cation exchange Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940073450 sudan red Drugs 0.000 description 1
- 150000003464 sulfur compounds Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 210000003384 transverse colon Anatomy 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/22—Ribonucleases RNAses, DNAses
-
- 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
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
-
- 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
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/916—Hydrolases (3) acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
- G01N2333/922—Ribonucleases (RNAses); Deoxyribonucleases (DNAses)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Marine Sciences & Fisheries (AREA)
- Gastroenterology & Hepatology (AREA)
- Endocrinology (AREA)
Abstract
Description
71-90: RELNRFDGSGPYSTLSSPQL
207-224: HWVIADGEDTTVRASTHC
187-206: CASLTKKRLDKLELRTEPGF
225-241: TYDRVVLHGERCRSLLH
254-269: LTEEEALNISDHYPVE
110-126: VLSSYVYNDEDDVFARE
を含みうる。
(a)DNaseをコードする内因性遺伝子の破壊
(b)DNase核酸を含有する転写物に対する少なくとも1つのアンチセンスRNAおよび/またはリボザイムの発現;
(c)DNase核酸のセンスおよび/または非転写可能mRNAの発現;
(d)DNaseポリペプチドに対する抗体の発現;
(e)DNaseの調節配列の機能的または非機能的コピーの組み込み;または
(f)DNase核酸を含む組換えDNase分子またはベクターの組み込み。
a) DNaseマーカー分子の検出のための試薬
b) バッファー、検出マーカー、担体物質および他のもの等の、検出反応を行うために一般的に用いられる試薬およびバッファー
d) 陽性対照反応を行うためのDNaseマーカー試料
を含む。
(a)本発明による本発明のDNaseポリペプチドを、スクリーニング対象の化合物と接触させること;および
(b)該化合物がポリペプチドの活性に影響するかどうかを調べること
を含み得る。
a. DNaseまたは該DNaseポリペプチドを発現する細胞を、
−細胞増殖の改変された調節
−DNaseポリペプチドの改変された活性
−改変された細胞分化
に応答して、検出可能なシグナルを提供することができる成分の存在下で、候補薬物と接触させ、タンパク質分解が可能な条件下でスクリーニングする工程、および
b. DNaseポリペプチド活性、細胞増殖または分化により生じたシグナルまたはシグナルの増加の存在または非存在を検出する工程(ここで、シグナルの存在または増加は、推定薬物であることを示す)を含む、癌腫およびその前駆病変の治療のための薬物候補を同定して得る方法に関する。
ホルマリンで固定化し、パラフィン包埋した結腸の組織試料の切片を、DNase Xに特異的な抗体を用いて免疫組織化学的に染色した。
casltkkrldklelrtepgf
に対して指向されるものである。
結腸の腺癌腫の外科的切除の過程で得た患者のリンパ節試料を用い、DNase X特異的結合剤との免疫反応性を示す細胞の存在を調べた。全部で、結腸癌腫を有する7患者由来の試料を含めた。
14 個体の集合を、本試験に含めた。7患者が、マンモグラフィ検査により、乳管にカルシウム沈着を有する(初期段階インサイチュ管癌腫であることを示す)と同定された。7個体は、乳の新形成病変を示す兆候を何ら示さなかった。
DNase Xタンパク質に対して指向されるモノクローナル抗体を用いると、DNase Xタンパク質の過剰発現が、免疫組織化学により解析したどの腫瘍存在物においても検出された。したがって、DNase Xタンパク質の過剰発現は、腫瘍における一般的な現象を表す。DNase Xタンパク質は、内在的酵素活性を有する可溶性タンパク質であるため、免疫組織化学レベルで見られる過剰発現が、腫瘍細胞に見られるDNase Xタンパク質の過剰発現は、腫瘍患者の体液における増強されたレベルのDNase Xタンパク質またはDNase活性をもたらし得ることを示す。
Claims (26)
- a)個体から試料を得る工程、
b)1つ以上のDNase分子のレベルを測定する工程;
c)該試料内のDNase分子のレベルと、試験対象の疾患に罹っていない相当する対象試料内の含有物とを比較する工程;
d)ここで疾患過程の診断または予後が、該障害または疾患過程の予後の指標として、少なくとも1つの単一のDNase分子またはDNase分子のセットの野生型レベルと比べた有意な変化を考察することから予測される、
を含む、癌およびその前駆病変の診断および/または疾患過程の予後のための方法。 - DNaseが、
a)DNaseI様1(DNase X)(NM_006730);
b)DNaseI様3(DNaseγとも呼ばれる)(AF047354);
c)DNaseI(AJ298844);
d)DNaseII(AB004574);
e)DNaseI様2(AK098028);
f)カスパーゼ活性化DNase(AB013918);
g)DNase KIAA0218;
h)DNaseI様DNase(AF274571);および
i)DFF-45(AF087573)
からなる群より選ばれる請求項1記載の方法。 - DNase分子の検出がDNase分子の特定領域の接近可能性の検出を含む請求項1または2記載の方法。
- DNaseの亜細胞局在化が測定される請求項1〜3いずれか記載の方法。
- 試料が、核酸、ポリペプチドまたはその断片を含有する液体、細胞または細胞細片、体液、組織試料および細胞試料から選ばれる前記請求項いずれか記載の方法。
- 組織が血液、血漿、血清、液体、リンパ液、骨髄、塗沫標本、洗浄液、洗浄液、分泌物、漏出液、滲出液、唾液、便、尿、精液、細胞試料および組織試料、穿刺物または生検材料である請求項5記載の方法。
- 癌が頭部および頸部の癌、呼吸器の癌、胃腸管の癌、皮膚およびその付属物の癌、中枢神経および末梢神経の癌、泌尿器系の癌、生殖器系の癌、内分泌系の癌、軟組織および骨の癌、リンパ球産生系の癌、乳癌、肺癌、子宮頸癌、結腸直腸癌または肛門性器の癌を含む群から選ばれる前記請求項いずれか記載の方法。
- DNase分子の発現の検出が、試料中のDNase酵素活性の検出により行われる請求項1〜7いずれか記載の方法。
- DNase分子の発現の検出が、検出対象分子への少なくとも1つのプローブの特異的な結合を用いて行われる請求項1〜7いずれか記載の方法。
- プローブが検出可能な標識である請求項9記載の方法。
- 標識が、放射性同位体、生物発光化合物、化学発光化合物、蛍光化合物、金属キレート、ビオチンもしくはジゴキシゲニンまたは酵素等の生物学的に関連する結合構造体からなる群より選ばれる請求項10記載の方法。
- 少なくとも1つのプローブが抗体、抗体の断片、抗原結合エピトープまたはミニ抗体である請求項9〜11記載の方法。
- 検出が、免疫細胞化学検出手順を含む請求項12記載の方法。
- マーカー核酸にハイブリダイズする少なくとも1つのプローブが、DNaseマーカー分子の検出のために使用される請求項9〜11記載の方法。
- 検出反応が核酸増幅反応を含む請求項14記載の方法。
- インサイチュ検出に使用される請求項14または15記載の方法。
- インビボまたはインビトロ分子イメージング法の課程において検出される前記請求項いずれか記載の方法。
- 障害の早期診断、最小残基疾患診断またはスクリーニング試験の課程において行われる前期請求項いずれか記載の方法。
- a)DNase核酸および/またはDNaseポリペプチドの検出のための試薬;
b)バッファー、検出マーカー、キャリア物質等の検出反応を行うために一般に使用される試薬および緩衝液
を少なくとも含有してなり、研究キット、診断キットまたはポイントオブケア試験キットである、前記請求項いずれか記載の方法を行うための試験キット。 - DNase核酸および/またはDNaseポリペプチドの検出のための試薬が該核酸および/またはポリペプチドに特異的に結合する薬剤である請求項19記載の試験キット。
- a)DNase活性、細胞増殖または細胞分化に応答して検出可能なシグナルを提供することができる成分の存在下で、DNaseポリペプチドまたは該ポリペプチドを発現する細胞と、スクリーニング対象の薬物候補とをDNase活性、細胞増殖または細胞分化における変化を可能にする条件下で接触させる工程および
b)DNase活性、細胞増殖または細胞分化から生じるシグナルの有無またはシグナルの増大を検出する工程、ここでシグナルの存在または増大は推定の薬物を示す、
を含む癌およびその前駆病変を治療するための薬物候補を同定し、得るための方法。 - 癌およびその前駆病変の検出および処置において使用するための、
a)DNaseポリペプチドに対する結合パートナー
b)DNaseポリペプチドのアクチベーター/アゴニストまたはインヒビター/アンタゴニスト;
c)DNaseポリペプチドの発現のアクチベーターまたはインヒビター; および
d)請求項21記載の方法により同定された薬物候補;
からなる群より選ばれる化合物。 - 癌およびその前駆病変を処置するのに有用な医薬の製造のための、
a)核酸またはポリペプチドである1つ以上のDNase分子;
b)DNaseポリペプチドの1つ以上のアクチベーター/アゴニストまたはインヒビター/アンタゴニスト;
c)DNaseポリペプチドの発現の1つ以上のアクチベーターまたはインヒビター;
d)DNaseポリペプチドの1つ以上の結合パートナー;および
e)請求項21記載の方法により同定可能な1つ以上の薬物候補;
を含む群より選ばれる化合物の使用。 - 癌が、頭部および頸部の癌、呼吸器の癌、胃腸管の癌、皮膚およびその付属物の癌、中枢神経および末梢神経の癌、泌尿器の癌、生殖器系の癌、内分泌系の癌、軟組織および骨の癌、リンパ球産生系および造血系の癌、乳癌、肺癌、子宮頸癌、結腸直腸癌または肛門性器の癌を含む群から選ばれる請求項23記載の使用。
- 癌およびその前駆病変を処置するための、
a)核酸またはポリペプチドである1つ以上のDNase分子;
b)DNaseポリペプチドの1つ以上のアクチベーター/アゴニストまたはインヒビター/アンタゴニスト;
c)DNaseポリペプチドの発現の1つ以上のアクチベーターまたはインヒビター;
d)DNaseポリペプチドの1つ以上の結合パートナー;
e)請求項21記載の方法により同定可能な1つ以上の薬物候補;
からなる群より選ばれる少なくとも1つの化合物を含有してなる医薬組成物。 - 請求項22記載の化合物または請求項25記載の医薬組成物を個体に投与することを含む癌およびその前駆病変の処置方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02102814A EP1431762B1 (en) | 2002-12-18 | 2002-12-18 | Compounds and methods for detection of carcinomas and their precursor lesions |
PCT/EP2003/051028 WO2004055514A1 (en) | 2002-12-18 | 2003-12-16 | Compounds and methods for detection of carcinomas and their precursor lesions |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2006510363A true JP2006510363A (ja) | 2006-03-30 |
JP2006510363A5 JP2006510363A5 (ja) | 2006-10-19 |
JP4527544B2 JP4527544B2 (ja) | 2010-08-18 |
Family
ID=32338157
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004560521A Expired - Lifetime JP4527544B2 (ja) | 2002-12-18 | 2003-12-16 | 癌およびその前駆病変の検出のための化合物および方法 |
Country Status (11)
Country | Link |
---|---|
US (2) | US20060121485A1 (ja) |
EP (1) | EP1431762B1 (ja) |
JP (1) | JP4527544B2 (ja) |
CN (1) | CN1726393B (ja) |
AT (1) | ATE360817T1 (ja) |
AU (1) | AU2003302964A1 (ja) |
CA (1) | CA2510150C (ja) |
DE (1) | DE60219809T2 (ja) |
ES (1) | ES2286201T3 (ja) |
HK (1) | HK1086331A1 (ja) |
WO (1) | WO2004055514A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008253188A (ja) * | 2007-04-04 | 2008-10-23 | Tokyo Univ Of Science | エンドサイトーシス依存性dna取り込み抑制剤、エンドサイトーシス依存性dna取り込み促進剤、ウイルス感染阻害剤、ウイルス感染予防剤、及びウイルス感染促進剤、並びに、遺伝子マーカー、モノクローナル抗体、ハイブリドーマ、及びそれらの使用方法。 |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2286201T3 (es) * | 2002-12-18 | 2007-12-01 | Coy, Johannes F., Dr. | Compuestos y procedimientos para la deteccion de carcinomas y sus lesiones precursoras. |
US8388951B2 (en) | 2003-07-14 | 2013-03-05 | Cls Therapeutics Limited | Method for treating systemic DNA mutation disease |
US8710012B2 (en) | 2003-07-14 | 2014-04-29 | Cls Therapeutics Limited | Method for treating oncological diseases |
EP2086642B1 (en) | 2006-10-18 | 2014-06-25 | Periness Ltd. | Dnase for the treatment of male sub-fertility |
US7734161B2 (en) * | 2007-04-19 | 2010-06-08 | Avago Technologies Ecbu Ip (Singapore) Pte. Ltd. | Image stabilization with adaptive shutter control |
US9360489B2 (en) * | 2007-06-11 | 2016-06-07 | Sutter Bay Hospitals | Method and kit for dynamic gene expression monitoring |
US10617743B2 (en) | 2014-06-19 | 2020-04-14 | Cls Therapeutics Limited | Method to improve safety and efficacy of anti-cancer therapy |
CN104267011A (zh) * | 2014-09-23 | 2015-01-07 | 中国科学院东北地理与农业生态研究所 | 一种转基因羊卵母细胞的筛选方法 |
RU2726131C2 (ru) | 2015-05-22 | 2020-07-09 | Дмитрий Дмитриевич Генкин | Внеклеточная днк в качестве терапевтической мишени при нейродегенерации |
CN107677823A (zh) * | 2016-08-02 | 2018-02-09 | 北京金沐医疗科技有限公司 | 一种用于检测肿瘤抗原的蛋白芯片试剂盒及其检测方法 |
CN107677820A (zh) * | 2016-08-02 | 2018-02-09 | 北京金沐医疗科技有限公司 | 一种检测肿瘤抗原的试剂盒及其检测方法 |
CN107677822A (zh) * | 2016-08-02 | 2018-02-09 | 北京金沐医疗科技有限公司 | 检测肿瘤标志物的荧光细胞计数检测试剂盒 |
WO2019143272A1 (en) | 2018-01-16 | 2019-07-25 | Cls Therapeutics Limited | Treatment of diseases by liver expression of an enzyme which has a deoxyribonuclease (dnase) activity |
CN109406771B (zh) * | 2018-10-26 | 2023-04-07 | 安徽大千生物工程有限公司 | 胱抑素c胶乳增强比浊法检测试剂盒及其制备使用方法 |
CN113314220B (zh) * | 2021-07-28 | 2021-11-02 | 江苏为真生物医药技术股份有限公司 | 疾病病程监控系统、计算机可读存储介质以及电子设备 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11507825A (ja) * | 1995-06-09 | 1999-07-13 | ドイチェス クレブスフォルシュンクスツェントルム スチフトゥング デス エッフェントリヒェン レヒツ | Dnアーゼ活性を有する蛋白質 |
WO2002088345A2 (en) * | 2001-04-11 | 2002-11-07 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Murine dnasex, medicament containing the same and non-human mammal comprising modified dnasex gene |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6335170B1 (en) * | 1999-02-22 | 2002-01-01 | Torben F. Orntoft | Gene expression in bladder tumors |
US20020052308A1 (en) * | 1999-03-12 | 2002-05-02 | Rosen Craig A. | Nucleic acids, proteins and antibodies |
WO2003053215A2 (en) * | 2001-11-07 | 2003-07-03 | The Board Of Trustees Of The University Of Arkansas | Diagnosis prognosis and identification of potential therapeutic targets of multiple myeloma based on gene expression profiling |
US20060199179A1 (en) * | 2002-06-19 | 2006-09-07 | Oncotherapy Science, Inc. | Method for diagnosis of colorectal tumors |
ES2286201T3 (es) * | 2002-12-18 | 2007-12-01 | Coy, Johannes F., Dr. | Compuestos y procedimientos para la deteccion de carcinomas y sus lesiones precursoras. |
-
2002
- 2002-12-18 ES ES02102814T patent/ES2286201T3/es not_active Expired - Lifetime
- 2002-12-18 AT AT02102814T patent/ATE360817T1/de active
- 2002-12-18 EP EP02102814A patent/EP1431762B1/en not_active Expired - Lifetime
- 2002-12-18 DE DE60219809T patent/DE60219809T2/de not_active Expired - Lifetime
-
2003
- 2003-12-16 CA CA2510150A patent/CA2510150C/en not_active Expired - Lifetime
- 2003-12-16 US US10/539,233 patent/US20060121485A1/en not_active Abandoned
- 2003-12-16 JP JP2004560521A patent/JP4527544B2/ja not_active Expired - Lifetime
- 2003-12-16 AU AU2003302964A patent/AU2003302964A1/en not_active Abandoned
- 2003-12-16 WO PCT/EP2003/051028 patent/WO2004055514A1/en active Application Filing
- 2003-12-16 CN CN2003801065094A patent/CN1726393B/zh not_active Expired - Fee Related
-
2006
- 2006-05-26 HK HK06106080.2A patent/HK1086331A1/xx not_active IP Right Cessation
-
2007
- 2007-10-29 US US11/927,274 patent/US8759004B2/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11507825A (ja) * | 1995-06-09 | 1999-07-13 | ドイチェス クレブスフォルシュンクスツェントルム スチフトゥング デス エッフェントリヒェン レヒツ | Dnアーゼ活性を有する蛋白質 |
WO2002088345A2 (en) * | 2001-04-11 | 2002-11-07 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Murine dnasex, medicament containing the same and non-human mammal comprising modified dnasex gene |
Non-Patent Citations (5)
Title |
---|
JPN5005013266, LOS MAREK, BIOCHEMISTRY, 20000627, V39 N25, P7365−7373, US, AMERICAN CHEMICAL SOCIETY * |
JPN5005013267, SHIOKAWA D, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 20000828, V275 N2, P343−349, US, ACADEMIC PRESS INC. * |
JPN5005013268, SHIOKAWA DAISUKE, BIOCHEMISTRY, 2001, V40 N1, P143−152, US, AMERICAN CHEMICAL SOCIETY * |
JPN5005013269, ECONOMIDOU−KARAOGLOU A, EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY, 198808, V24 N8, P1337−1343, GB * |
JPN5005013270, TSUTSUMI S, CANCER LETTERS, 20001016, V159 N1, P109−112, IE * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008253188A (ja) * | 2007-04-04 | 2008-10-23 | Tokyo Univ Of Science | エンドサイトーシス依存性dna取り込み抑制剤、エンドサイトーシス依存性dna取り込み促進剤、ウイルス感染阻害剤、ウイルス感染予防剤、及びウイルス感染促進剤、並びに、遺伝子マーカー、モノクローナル抗体、ハイブリドーマ、及びそれらの使用方法。 |
Also Published As
Publication number | Publication date |
---|---|
ATE360817T1 (de) | 2007-05-15 |
DE60219809D1 (de) | 2007-06-06 |
CA2510150A1 (en) | 2004-07-01 |
WO2004055514A1 (en) | 2004-07-01 |
EP1431762B1 (en) | 2007-04-25 |
AU2003302964A1 (en) | 2004-07-09 |
CN1726393B (zh) | 2010-04-28 |
CN1726393A (zh) | 2006-01-25 |
DE60219809T2 (de) | 2008-01-17 |
ES2286201T3 (es) | 2007-12-01 |
US8759004B2 (en) | 2014-06-24 |
US20080234393A1 (en) | 2008-09-25 |
US20060121485A1 (en) | 2006-06-08 |
JP4527544B2 (ja) | 2010-08-18 |
EP1431762A1 (en) | 2004-06-23 |
CA2510150C (en) | 2017-11-07 |
HK1086331A1 (en) | 2006-09-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8759004B2 (en) | Compounds and methods for detection of carcinomas and their precursor lesions | |
EP1998177A2 (en) | Compositions and methods for diagnosing and treating colon cancers | |
JP2011036247A (ja) | 子宮頸癌の同定、評価、予防および治療を行うための組成物、キットおよび方法 | |
JP2010246558A (ja) | 乳癌の同定、評価、予防、および治療のための組成物、キットおよび方法 | |
JP2008509673A (ja) | ヒト前立腺癌の同定、評価、予防および治療のための遺伝子、組成物、キットおよび方法 | |
JP2005508144A (ja) | 卵巣癌の診断方法、卵巣癌のモジュレーターをスクリーニングする組成物及び方法 | |
WO2004074510A1 (en) | Methods of diagnosis and prognosis of pancreatic cancer | |
JP5380075B2 (ja) | がん関連抗原 | |
KR20070073802A (ko) | Wnt 단백질 및 암의 검출 및 치료 | |
KR20060120652A (ko) | 난소암의 확인, 평가, 예방 및 치료를 위한 핵산 분자 및단백질 | |
WO2014061419A1 (ja) | 新規癌マーカーおよびその利用 | |
JP2003524017A (ja) | タンパク質 | |
JP2003507027A (ja) | タンパク質、遺伝子ならびに乳癌の診断及び処置へのこれらの使用 | |
EP1426442A1 (en) | Marker molecules associated with colorectal lesions | |
US7883896B2 (en) | Marker molecules associated with lung tumors | |
JP2006506645A (ja) | 癌の存在またはステージの診断方法 | |
EP1395830B1 (en) | Bcmp-101, a cancer associated protein | |
EP1395829A2 (en) | Cancer associated protein |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060904 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060904 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090703 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091002 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20091126 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100225 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100415 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100415 |
|
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: 20100512 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100603 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130611 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4527544 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140611 Year of fee payment: 4 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |