JP2006504104A - 腫瘍形成を診断するための方法及びキット - Google Patents
腫瘍形成を診断するための方法及びキット Download PDFInfo
- Publication number
- JP2006504104A JP2006504104A JP2004548520A JP2004548520A JP2006504104A JP 2006504104 A JP2006504104 A JP 2006504104A JP 2004548520 A JP2004548520 A JP 2004548520A JP 2004548520 A JP2004548520 A JP 2004548520A JP 2006504104 A JP2006504104 A JP 2006504104A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- patient
- biological fluid
- cells
- concentration
- 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 78
- 230000005740 tumor formation Effects 0.000 title claims description 20
- 239000013060 biological fluid Substances 0.000 claims abstract description 65
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 25
- 230000002622 anti-tumorigenesis Effects 0.000 claims abstract description 24
- 101710114165 Progranulin Proteins 0.000 claims abstract description 21
- 102100037632 Progranulin Human genes 0.000 claims abstract description 21
- 230000000381 tumorigenic effect Effects 0.000 claims abstract description 21
- 231100000588 tumorigenic Toxicity 0.000 claims abstract description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 70
- 201000011510 cancer Diseases 0.000 claims description 41
- 238000011282 treatment Methods 0.000 claims description 38
- 210000004408 hybridoma Anatomy 0.000 claims description 11
- 230000000259 anti-tumor effect Effects 0.000 claims description 7
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 3
- 238000002405 diagnostic procedure Methods 0.000 claims 1
- 210000002966 serum Anatomy 0.000 abstract description 36
- 210000004369 blood Anatomy 0.000 abstract description 9
- 239000008280 blood Substances 0.000 abstract description 9
- 210000002700 urine Anatomy 0.000 abstract description 6
- 210000003296 saliva Anatomy 0.000 abstract description 3
- 210000002381 plasma Anatomy 0.000 abstract 1
- 108090000288 Glycoproteins Proteins 0.000 description 342
- 102000003886 Glycoproteins Human genes 0.000 description 339
- 210000004027 cell Anatomy 0.000 description 140
- 230000014509 gene expression Effects 0.000 description 70
- 239000000523 sample Substances 0.000 description 69
- 108090000765 processed proteins & peptides Proteins 0.000 description 47
- 210000001519 tissue Anatomy 0.000 description 46
- 230000000692 anti-sense effect Effects 0.000 description 41
- 108090000623 proteins and genes Proteins 0.000 description 40
- 102000004196 processed proteins & peptides Human genes 0.000 description 39
- 241000282414 Homo sapiens Species 0.000 description 38
- 230000001965 increasing effect Effects 0.000 description 36
- 102000004169 proteins and genes Human genes 0.000 description 30
- 229920001184 polypeptide Polymers 0.000 description 29
- 235000018102 proteins Nutrition 0.000 description 29
- 108020004999 messenger RNA Proteins 0.000 description 26
- 239000000427 antigen Substances 0.000 description 24
- 108091007433 antigens Proteins 0.000 description 24
- 102000036639 antigens Human genes 0.000 description 24
- 201000010099 disease Diseases 0.000 description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 238000001514 detection method Methods 0.000 description 23
- 206010006187 Breast cancer Diseases 0.000 description 22
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 22
- 208000026310 Breast neoplasm Diseases 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 21
- 239000002299 complementary DNA Substances 0.000 description 21
- 230000000694 effects Effects 0.000 description 20
- 238000003556 assay Methods 0.000 description 19
- 238000001574 biopsy Methods 0.000 description 19
- 150000007523 nucleic acids Chemical class 0.000 description 19
- 238000002965 ELISA Methods 0.000 description 17
- 230000027455 binding Effects 0.000 description 17
- 102000039446 nucleic acids Human genes 0.000 description 17
- 108020004707 nucleic acids Proteins 0.000 description 17
- 108060003393 Granulin Proteins 0.000 description 16
- 102000017941 granulin Human genes 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 230000003472 neutralizing effect Effects 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 14
- 239000005557 antagonist Substances 0.000 description 14
- 239000000074 antisense oligonucleotide Substances 0.000 description 14
- 238000012230 antisense oligonucleotides Methods 0.000 description 14
- 239000012634 fragment Substances 0.000 description 14
- 239000003102 growth factor Substances 0.000 description 14
- 108091034117 Oligonucleotide Proteins 0.000 description 13
- 125000003275 alpha amino acid group Chemical group 0.000 description 13
- 230000001833 anti-estrogenic effect Effects 0.000 description 13
- 230000004071 biological effect Effects 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 239000000328 estrogen antagonist Substances 0.000 description 13
- 230000012010 growth Effects 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 229940046836 anti-estrogen Drugs 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 239000002773 nucleotide Substances 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 230000003287 optical effect Effects 0.000 description 12
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 102000004877 Insulin Human genes 0.000 description 11
- 108090001061 Insulin Proteins 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 229940125396 insulin Drugs 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 9
- 101001027325 Mus musculus Progranulin Proteins 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 239000012530 fluid Substances 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 9
- 230000014616 translation Effects 0.000 description 9
- 108020005544 Antisense RNA Proteins 0.000 description 8
- 101001027324 Homo sapiens Progranulin Proteins 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000003184 complementary RNA Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 238000009396 hybridization Methods 0.000 description 8
- 238000003018 immunoassay Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 241000282412 Homo Species 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 230000003305 autocrine Effects 0.000 description 7
- 230000010261 cell growth Effects 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
- 230000035755 proliferation Effects 0.000 description 7
- 238000013519 translation Methods 0.000 description 7
- 230000004614 tumor growth Effects 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- 238000011735 C3H mouse Methods 0.000 description 6
- 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 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 229940027941 immunoglobulin g Drugs 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 230000003211 malignant effect Effects 0.000 description 6
- -1 ricinyl Chemical group 0.000 description 6
- 102220238200 rs1238996324 Human genes 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 108010001857 Cell Surface Receptors Proteins 0.000 description 5
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000012472 biological sample Substances 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 102000015694 estrogen receptors Human genes 0.000 description 5
- 108010038795 estrogen receptors Proteins 0.000 description 5
- 238000001415 gene therapy Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 102000006240 membrane receptors Human genes 0.000 description 5
- YIEDSISPYKQADU-UHFFFAOYSA-N n-acetyl-n-[2-methyl-4-[(2-methylphenyl)diazenyl]phenyl]acetamide Chemical compound C1=C(C)C(N(C(C)=O)C(=O)C)=CC=C1N=NC1=CC=CC=C1C YIEDSISPYKQADU-UHFFFAOYSA-N 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 229960001603 tamoxifen Drugs 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 241000701022 Cytomegalovirus Species 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 4
- 101710203190 Mid1-interacting protein 1 Proteins 0.000 description 4
- 102100028338 Mid1-interacting protein 1 Human genes 0.000 description 4
- 239000000020 Nitrocellulose Substances 0.000 description 4
- 101710163270 Nuclease Proteins 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 210000000069 breast epithelial cell Anatomy 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 210000002751 lymph Anatomy 0.000 description 4
- 230000036210 malignancy Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 229920001220 nitrocellulos Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000003127 radioimmunoassay Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 3
- 102100036519 Gastrin-releasing peptide Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 3
- 238000000636 Northern blotting Methods 0.000 description 3
- 108091036066 Three prime untranslated region Proteins 0.000 description 3
- 239000003443 antiviral agent Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 150000001720 carbohydrates Chemical group 0.000 description 3
- 239000003636 conditioned culture medium Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 231100001221 nontumorigenic Toxicity 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 3
- 229960004622 raloxifene Drugs 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 238000003118 sandwich ELISA Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000005030 transcription termination Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 101000972324 Cynodon dactylon Leaf protein Proteins 0.000 description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 2
- 108090001053 Gastrin releasing peptide Proteins 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 101000969137 Mus musculus Metallothionein-1 Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 102220493212 Small nuclear ribonucleoprotein E_A14R_mutation Human genes 0.000 description 2
- 230000002293 adipogenic effect Effects 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 239000003145 cytotoxic factor Substances 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 238000013188 needle biopsy Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 208000037821 progressive disease Diseases 0.000 description 2
- 230000026267 regulation of growth Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000003153 stable transfection Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 239000000439 tumor marker Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 1
- FVFVNNKYKYZTJU-UHFFFAOYSA-N 6-chloro-1,3,5-triazine-2,4-diamine Chemical group NC1=NC(N)=NC(Cl)=N1 FVFVNNKYKYZTJU-UHFFFAOYSA-N 0.000 description 1
- 102100040768 60S ribosomal protein L32 Human genes 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 108020004491 Antisense DNA Proteins 0.000 description 1
- 108010051479 Bombesin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 229940102550 Estrogen receptor antagonist Drugs 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- 108010001515 Galectin 4 Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101000672453 Homo sapiens 60S ribosomal protein L32 Proteins 0.000 description 1
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 1
- 101000766306 Homo sapiens Serotransferrin Proteins 0.000 description 1
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 1
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101000578878 Mus musculus Mid1-interacting protein 1 Proteins 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000772415 Neovison vison Species 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 239000003816 antisense DNA Substances 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 229940078010 arimidex Drugs 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- DNDCVAGJPBKION-DOPDSADYSA-N bombesin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC2=CC=CC=C2C=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1NC(=O)CC1)C(C)C)C1=CN=CN1 DNDCVAGJPBKION-DOPDSADYSA-N 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- YTRQFSDWAXHJCC-UHFFFAOYSA-N chloroform;phenol Chemical compound ClC(Cl)Cl.OC1=CC=CC=C1 YTRQFSDWAXHJCC-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940087861 faslodex Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- ZJYYHGLJYGJLLN-UHFFFAOYSA-N guanidinium thiocyanate Chemical compound SC#N.NC(N)=N ZJYYHGLJYGJLLN-UHFFFAOYSA-N 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 238000012606 in vitro cell culture Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000000691 measurement method Methods 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
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 230000000683 nonmetastatic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 150000004713 phosphodiesters Chemical group 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000009465 prokaryotic expression Effects 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 101150079601 recA gene Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229960003454 tamoxifen citrate Drugs 0.000 description 1
- FQZYTYWMLGAPFJ-OQKDUQJOSA-N tamoxifen citrate Chemical compound [H+].[H+].[H+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 FQZYTYWMLGAPFJ-OQKDUQJOSA-N 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/026—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a baculovirus
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
いくつかの公表物を括弧内のアラビア数字によって本明細書中で参照する。特許請求の範囲の直前の本明細書の最後にこれらの参照の全ての引用を見ることができる。
多細胞生物における細胞の増殖及び分化は、高度に調節されたプロセスを受ける。癌細胞を区別する特徴はこのプロセスに対する制御が無いことであって、増殖及び分化が調節されなくなり、結果として制御されない増殖が生じる。正常細胞及び腫瘍細胞の間のこの違いをより理解することに対して多大な研究努力が向けられてきた。焦点が当てられている研究の一領域は成長因子であり、より具体的にはオートクリン増殖刺激である。
本発明者は、正常細胞では厳格に調節された形式で発現される糖タンパク質(GP88)が正常な細胞由来の腫瘍形成能の高い細胞では過剰発現され、かつ、調節されないこと、腫瘍形成細胞に厳格に(stringently)必要とされる増殖刺激物質としてGP88が作用すること、及び腫瘍形成細胞でのGP88の発現又は作用を阻害することによって過剰産生細胞の腫瘍形成特性が阻害されることを今、予想外にも発見した。
ここで、以下の実施例とともに本発明の要点を説明するのに役立つ現在好ましい本発明の実施態様について詳細に参照する。
本発明は、GP88の変化した(増加した)発現に関連した疾患の治療及び診断に有用なGP88並びに抗腫瘍及び抗ウイルス組成物に関する。あるいは、本発明は、GP88に対する増加した反応に関連した疾患の治療及び診断に用いられる。3つの細胞系からなるマウスモデル系を用いて、本発明者によって、GP88を過剰発現する細胞が腫瘍を形成することが示された。親細胞系1246は、合成(defined)培地中でインスリンによる厳格な調節下で増殖して脂肪細胞へと分化するC3Hマウス脂肪生成細胞系である。1246細胞は、高い細胞密度で注射したときでさえ、同系の動物(C3Hマウス)で腫瘍を形成することはできない。インスリン非依存性細胞系1246−3Aを、インスリンなしの培地で維持された1246細胞から単離した。106個を同系マウスに皮下注射したとき、1246−3A細胞は分化する能力を失って腫瘍を形成した。in vitro- in vivoシャトル技術により、腫瘍形成能の高い細胞系PCが1246−3A細胞から生成された。104個の細胞を同系マウスに注射したときに、PC細胞は腫瘍を形成した。
PC:対照非トランスフェクション細胞
P−14:空のベクターでトランスフェクションした対照PC細胞
ASGP88:GP88アンチセンスcDNAを含有する発現ベクターでトランスフェクションしたPC細胞
45日目に腫瘍を切除し、重量測定した。−−−は、腫瘍形成がなかったことを示す。
本発明は、GP88の増加した発現に関連する疾患の治療及び予防用組成物を提供する。これは、GP88の増加した反応に関連する疾患の治療及び診断にも適用される。本発明の組成物には、GP88の生物活性を中和する抗GP88抗体が含まれる。
本発明の好ましい実施態様は、生物液中のGP88を検出する方法及びキットに関する。上記の通り、癌細胞は高いレベルのGP88を発現する。本発明は、GP88を約0.1ng/mlの低さの濃度において生物液中で検出することができることを実証している。上記の通り、GP88は癌細胞中で過剰発現し、高いレベルのGP88は腫瘍形成を示している。典型的には、腫瘍マーカーの存在を検出するためには組織試料又は生検が必要である。例えば、乳癌患者には、特定の腫瘍マーカーが存在しているかの決定の検査のために乳房組織試料を取り出すため、しばしば針生検手順が施される。生検手順は、任意の外科手術手順と同様に、患者への増加した危険性と関連している。生検手順は、特に、腫瘍形成の増加した危険性に関連している。
本発明は、GP88アンチセンス成分も提供する。細胞中でのアンチセンスRNAの構成性発現は20種より多くの遺伝子の発現を阻害することが示され、列記は増え続けている。アンチセンス効果の可能な機構は翻訳の遮断又はスプライシングの妨害であり、双方ともin vitroで観察されている。スプライシングの妨害によって、保存性が低いイントロン配列が使用されることとなり、したがってより大きな特異性が生じ、ある種の遺伝子産物の発現は阻害されるが別の種ではそのホモログは阻害されないこととなる。
本発明は、他の哺乳動物DNA配列を実質的に有さない組換えGP88ポリペプチド又はその機能性誘導体を発現するためのDNA発現系にも関する。そのようなDNAは、二重鎖又は一本鎖であることができる。DNA配列は、好ましくは、別のポリヌクレオチドとのハイブリダイゼーションを可能とするために約20個以上のヌクレオチドを有しなければならない。GP88タンパク質又はその同族体若しくは機能性誘導体をコードする配列以外の配列とのハイブリダイゼーションが無いことによって特徴付けられるより高い特異性のハイブリダイゼーションを達成するためには、長さが少なくとも50個のヌクレオチドが好ましい。
17人の正常かつ健康なヒトボランティアから血清試料を得た。ヒト血清試料中のGP88濃度を酵素結合免疫吸着アッセイ(ELISA)によって3つ組で測定した。30%グリセロール及び1%ミルク−PBSの溶液に希釈した組換えGP88から0、0.1、0.25、0.5、1、3、10、及び20ng/mlの濃度で標準のGP88試料を調製した。マイクロタイタープレート上の100マイクロリットルのウェルを1ミリリットルあたり10マイクログラムの抗ヒトGP88モノクローナル抗体6B3(リン酸緩衝生理食塩水(PBS)中の0.78mg/mlの6B3抗体)でコーティングし、4℃で一晩インキュベーションした。ウェルをPBSで洗浄し、続いて抗ヒトPCDGFポリクローナル(IgG分画)を各ウェルに3マイクログラム/mlの濃度で37℃で1.5時間添加した。各ウェルへの検出抗体(セイヨウワサビペルオキシダーゼ(HRP)−ヤギ−ウサギ−IgG)の添加前に、ウェルをPBS中で洗浄した。TMB(基質)を添加し、試料とともに1時間インキュベーションした。620ナノメートルの波長で設定したELISA分光計読み取り器を用いて試料の光学濃度を決定した。各試料中のGP88量(x軸)に対して標準のGP88試料の光学濃度(y軸)をプロットし、標準曲線を作成した(図16)。未知試料中のGP88の濃度は、光学濃度を測定し、標準曲線(図16)を用いてGP88濃度を決定することによって決定した。表3は、17人の健康なヒトボランティアの各人のGP88血清試料濃度を提供するものである。
Claims (10)
- 生物液を抗GP88抗体又は抗体フラグメントと接触させる工程及びGP88の濃度を測定する工程を含み、ここで1ミリリットルあたりのGP88濃度が約0.1〜約10ナノグラムの低さでもGP88を検出することが可能である、生物液中のGP88濃度の高感度測定方法。
- 前記GP88抗体が、ATCC受託番号6B3PTA−5262及びATCC受託番号6B2PTA−5261から成る群から選択されるハイブリドーマ細胞株から産生される、請求項1に記載の方法。
- 前記抗GP88抗体がモノクローナル抗体である、請求項1に記載の方法。
- 患者から採取した第1の生物液試料中のGP88タンパク質レベルを測定する工程、前記患者から採取した第2の生物液試料中のGP88タンパク質レベルを測定する工程、及び前記第2の生物液試料中の測定されたGP88タンパク質レベルが前記第1の生物液試料中のレベルよりも腫瘍形成能を示すのに十分な程に高い量であるかを判定することによって腫瘍形成を診断する工程を含む、腫瘍形成の診断方法。
- 抗GP88抗体を用いて生物液試料中のGP88レベルを測定する工程、及び前記生物液試料中のGP88レベルが腫瘍形成を示すのに十分であるかを判定する工程を含む、腫瘍形成の診断方法。
- 患者から得た生物液試料中のGP88濃度を測定する工程、及び前記生物液試料中のGP88濃度が、前記患者が抗腫瘍形成治療に反応していないか又は反応性でないかを示すのに十分であるかを判定する工程を含む、患者が抗腫瘍形成治療に反応しているか反応性であるかの判定方法。
- 患者から得た生物液試料中のGP88濃度を決定する工程、及び前記生物液試料中のGP88濃度が腫瘍形成を示すのに十分である場合に、癌を治療又は予防するのに十分な量の抗腫瘍形成治療を投与する工程を含む、患者における癌再発の治療又は予防方法。
- 容器及び抗ヒトGP88抗体又は抗体フラグメントを含有する、腫瘍形成診断のためのキット。
- 容器及び抗ヒトGP88抗体を含有する、患者が抗腫瘍形成治療に反応しているか又は反応性であるかを判定するためのキット。
- ATCC受託番号PTA−5262、ATCC受託番号PTA−5261、ATCC番号PTA−5589、ATCC番号PTA−5593、ATCC番号PTA−5259、ATCC番号PTA−5260、及びATCC番号PTA−5591から成る群から選択されるハイブリドーマ細胞株から産生される抗GP88抗体。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/281,160 US7091047B2 (en) | 1997-05-23 | 2002-10-28 | Methods and kits for diagnosing tumorigenicity |
PCT/US2003/034146 WO2004039244A2 (en) | 2002-10-28 | 2003-10-27 | Methods and kits for diagnosing tumorigenicity |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008261912A Division JP4763032B2 (ja) | 2002-10-28 | 2008-10-08 | 癌の存在又は不存在を判定する方法及びキット |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2006504104A true JP2006504104A (ja) | 2006-02-02 |
JP4242836B2 JP4242836B2 (ja) | 2009-03-25 |
Family
ID=32228759
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004548520A Expired - Lifetime JP4242836B2 (ja) | 2002-10-28 | 2003-10-27 | 腫瘍形成を診断するための方法及びキット |
JP2008261912A Expired - Fee Related JP4763032B2 (ja) | 2002-10-28 | 2008-10-08 | 癌の存在又は不存在を判定する方法及びキット |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008261912A Expired - Fee Related JP4763032B2 (ja) | 2002-10-28 | 2008-10-08 | 癌の存在又は不存在を判定する方法及びキット |
Country Status (8)
Country | Link |
---|---|
US (1) | US7091047B2 (ja) |
EP (1) | EP1563308B1 (ja) |
JP (2) | JP4242836B2 (ja) |
AT (1) | ATE529743T1 (ja) |
AU (2) | AU2003284190B2 (ja) |
CA (1) | CA2504178C (ja) |
ES (1) | ES2395125T3 (ja) |
WO (1) | WO2004039244A2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012502280A (ja) * | 2008-09-05 | 2012-01-26 | エー アンド ジー ファーマシューティカル,インコーポレイテッド | 癌の診断方法ならびに癌患者の全生存期間および無病生存期間の決定方法 |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030215445A1 (en) | 1997-05-23 | 2003-11-20 | Ginette Serrero | Methods and compositions for inhibiting the growth of hematopoietic malignant cells |
US8512960B2 (en) * | 1997-05-23 | 2013-08-20 | A&G Pharmaceutical, Inc. | 88kDa tumorigenic growth factor and antagonists |
US20100111928A1 (en) * | 1997-05-23 | 2010-05-06 | A & G Pharmaceutical, Inc. | Methods and kits for diagnosis tumorgenicity |
US6309826B1 (en) * | 1997-05-23 | 2001-10-30 | Ginette Serrero | 88kDa tumorigenic growth factor and antagonists |
US7411045B2 (en) * | 2002-11-19 | 2008-08-12 | A&G Pharmaceutical, Inc. | Autocrine growth factor receptor antibodies and methods |
US7651854B2 (en) * | 2003-02-26 | 2010-01-26 | A & G Pharmaceutical, Inc. | Methods for increasing the proliferation of B cells |
EP1849480A3 (en) * | 2003-06-23 | 2013-06-26 | A & G Pharmaceutical, Inc. | Compositions and methods for restoring sensitivity of tumor cells to antitumor therapy and inducing apoptosis |
WO2005009363A2 (en) * | 2003-07-21 | 2005-02-03 | Medimmune, Inc. | Treatment of pre-cancerous conditions and prevention of cancer using pcdgf-based therapies |
ES2426916T3 (es) * | 2003-08-01 | 2013-10-25 | A & G Pharmaceutical, Inc. | Composiciones y procedimientos para restaurar la sensibilidad al tratamiento con antagonistas de HER2 |
US8968210B2 (en) | 2008-10-01 | 2015-03-03 | Covidien LLP | Device for needle biopsy with integrated needle protection |
US11298113B2 (en) | 2008-10-01 | 2022-04-12 | Covidien Lp | Device for needle biopsy with integrated needle protection |
US9332973B2 (en) | 2008-10-01 | 2016-05-10 | Covidien Lp | Needle biopsy device with exchangeable needle and integrated needle protection |
US9782565B2 (en) | 2008-10-01 | 2017-10-10 | Covidien Lp | Endoscopic ultrasound-guided biliary access system |
US9186128B2 (en) | 2008-10-01 | 2015-11-17 | Covidien Lp | Needle biopsy device |
EA035293B1 (ru) | 2015-05-01 | 2020-05-26 | ОЭнЭл ТЕРАПЬЮТИКС, ИНК. | Пептидные композиции и способы использования |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5416192A (en) | 1990-04-03 | 1995-05-16 | Bristol-Myers Squibb Company | Epithelins: novel cysteine-rich growth modulating proteins |
WO1993015195A1 (en) | 1992-02-03 | 1993-08-05 | Samuel Solomon | Granulins from leukocytes |
US6881548B2 (en) * | 1997-05-23 | 2005-04-19 | A&G Pharmaceutical, Inc. | Methods and kits for diagnosing tumorigenicity and determining resistance to the antineoplastic effects of antiestrogen therapy |
US6309826B1 (en) * | 1997-05-23 | 2001-10-30 | Ginette Serrero | 88kDa tumorigenic growth factor and antagonists |
US6511986B2 (en) | 2000-08-11 | 2003-01-28 | Wyeth | Method of treating estrogen receptor positive carcinoma |
US20110159527A1 (en) * | 2008-06-16 | 2011-06-30 | Michael Gebhard Schlossmacher | Methods and kits for diagnosing neurodegenerative disease |
-
2002
- 2002-10-28 US US10/281,160 patent/US7091047B2/en not_active Expired - Lifetime
-
2003
- 2003-10-27 AU AU2003284190A patent/AU2003284190B2/en not_active Ceased
- 2003-10-27 JP JP2004548520A patent/JP4242836B2/ja not_active Expired - Lifetime
- 2003-10-27 CA CA2504178A patent/CA2504178C/en not_active Expired - Lifetime
- 2003-10-27 EP EP03776580A patent/EP1563308B1/en not_active Expired - Lifetime
- 2003-10-27 AT AT03776580T patent/ATE529743T1/de not_active IP Right Cessation
- 2003-10-27 WO PCT/US2003/034146 patent/WO2004039244A2/en active Search and Examination
- 2003-10-27 ES ES03776580T patent/ES2395125T3/es not_active Expired - Lifetime
-
2008
- 2008-10-08 JP JP2008261912A patent/JP4763032B2/ja not_active Expired - Fee Related
-
2010
- 2010-11-29 AU AU2010246504A patent/AU2010246504B2/en not_active Ceased
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012502280A (ja) * | 2008-09-05 | 2012-01-26 | エー アンド ジー ファーマシューティカル,インコーポレイテッド | 癌の診断方法ならびに癌患者の全生存期間および無病生存期間の決定方法 |
JP2015158498A (ja) * | 2008-09-05 | 2015-09-03 | エー アンド ジー ファーマシューティカル,インコーポレイテッド | 癌の診断方法ならびに癌患者の全生存期間および無病生存期間の決定方法 |
Also Published As
Publication number | Publication date |
---|---|
CA2504178C (en) | 2020-12-15 |
EP1563308A4 (en) | 2006-11-29 |
AU2003284190A1 (en) | 2004-05-25 |
EP1563308A2 (en) | 2005-08-17 |
JP2009109489A (ja) | 2009-05-21 |
AU2003284190B2 (en) | 2010-09-02 |
JP4763032B2 (ja) | 2011-08-31 |
US20030108950A1 (en) | 2003-06-12 |
CA2504178A1 (en) | 2004-05-13 |
WO2004039244A3 (en) | 2005-05-19 |
ATE529743T1 (de) | 2011-11-15 |
US7091047B2 (en) | 2006-08-15 |
AU2010246504A1 (en) | 2010-12-23 |
JP4242836B2 (ja) | 2009-03-25 |
AU2010246504B2 (en) | 2011-09-22 |
ES2395125T3 (es) | 2013-02-08 |
WO2004039244A2 (en) | 2004-05-13 |
EP1563308B1 (en) | 2011-10-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4763032B2 (ja) | 癌の存在又は不存在を判定する方法及びキット | |
JP2015227369A (ja) | 抗エストロゲン療法の抗新生物作用に対して耐性を示す患者における腫瘍細胞成長を阻害、予防又は低減するための方法及び組成物 | |
AU2002312462A1 (en) | Methods and compositions for inhibiting, preventing, or reducing tumor cell growth in patients resistant to the antineoplastic effects of antiestrogen therapy | |
AU2002315060A1 (en) | Diagnosing tumorigenicity and determining resistance to anticancer therapy | |
JP2007524622A (ja) | 抗癌治療に対する腫瘍細胞の感受性を回復させてアポトーシスを誘導するための組成物及び方法 | |
AU2003295601B2 (en) | Autocrine growth factor receptor antibodies and methods | |
US20100111928A1 (en) | Methods and kits for diagnosis tumorgenicity | |
AU2007229401B2 (en) | Methods and kits for diagnosing tumorigenicity and determining resistance to the antineoplastic efffects of antiestrogen therapy |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061017 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20071030 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080130 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080206 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080229 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080307 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080331 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080407 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080417 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20080610 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20080908 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081008 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20081117 |
|
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: 20081209 |
|
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: 20081225 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120109 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4242836 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: 20130109 Year of fee payment: 4 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140109 Year of fee payment: 5 |
|
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 |