ES2694018T3 - Composiciones y métodos para el tratamiento y el diagnóstico del cáncer - Google Patents

Info

Publication number

ES2694018T3

ES2694018T3 ES15178099.6T ES15178099T ES2694018T3 ES 2694018 T3 ES2694018 T3 ES 2694018T3 ES 15178099 T ES15178099 T ES 15178099T ES 2694018 T3 ES2694018 T3 ES 2694018T3

Authority

ES

Spain

Prior art keywords

protein

human

cancer

immunoglobulin molecule

lgr

Prior art date

2007-07-02

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.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 206010028980 Neoplasm Diseases 0.000 title claims abstract description 471
• 201000011510 cancer Diseases 0.000 title claims description 260
• 238000000034 method Methods 0.000 title claims description 157
• 238000011282 treatment Methods 0.000 title claims description 52
• 239000000203 mixture Substances 0.000 title description 49
• 238000003745 diagnosis Methods 0.000 title description 22
• 108090000623 proteins and genes Proteins 0.000 claims abstract description 313
• 241000282414 Homo sapiens Species 0.000 claims abstract description 211
• 102000004169 proteins and genes Human genes 0.000 claims abstract description 209
• 101001063456 Homo sapiens Leucine-rich repeat-containing G-protein coupled receptor 5 Proteins 0.000 claims abstract description 164
• 102100031036 Leucine-rich repeat-containing G-protein coupled receptor 5 Human genes 0.000 claims abstract description 145
• 108091006332 Leucine-rich repeat-containing G-protein-coupled receptors Proteins 0.000 claims abstract description 140
• 102000037126 Leucine-rich repeat-containing G-protein-coupled receptors Human genes 0.000 claims abstract description 140
• 230000027455 binding Effects 0.000 claims abstract description 81
• 108060003951 Immunoglobulin Proteins 0.000 claims abstract description 70
• 102000018358 immunoglobulin Human genes 0.000 claims abstract description 70
• 230000012010 growth Effects 0.000 claims abstract description 28
• 239000000427 antigen Substances 0.000 claims abstract description 26
• 108091007433 antigens Proteins 0.000 claims abstract description 26
• 102000036639 antigens Human genes 0.000 claims abstract description 26
• 101000981765 Homo sapiens Leucine-rich repeat-containing G-protein coupled receptor 6 Proteins 0.000 claims abstract description 24
• 102100024140 Leucine-rich repeat-containing G-protein coupled receptor 6 Human genes 0.000 claims abstract description 21
• 102000005962 receptors Human genes 0.000 claims abstract description 21
• 108020003175 receptors Proteins 0.000 claims abstract description 21
• 101001063463 Homo sapiens Leucine-rich repeat-containing G-protein coupled receptor 4 Proteins 0.000 claims abstract description 19
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 18
• 102100031035 Leucine-rich repeat-containing G-protein coupled receptor 4 Human genes 0.000 claims abstract description 15
• 230000009870 specific binding Effects 0.000 claims abstract description 10
• 101000887490 Homo sapiens Guanine nucleotide-binding protein G(z) subunit alpha Proteins 0.000 claims abstract 5
• 102000052301 human GNAZ Human genes 0.000 claims abstract 5
• 210000004027 cell Anatomy 0.000 claims description 223
• 230000014509 gene expression Effects 0.000 claims description 137
• 210000004881 tumor cell Anatomy 0.000 claims description 92
• 101000825954 Homo sapiens R-spondin-1 Proteins 0.000 claims description 74
• 230000011664 signaling Effects 0.000 claims description 74
• 102100022762 R-spondin-1 Human genes 0.000 claims description 70
• 239000003795 chemical substances by application Substances 0.000 claims description 63
• 108060000903 Beta-catenin Proteins 0.000 claims description 49
• 102000015735 Beta-catenin Human genes 0.000 claims description 49
• 208000029742 colonic neoplasm Diseases 0.000 claims description 45
• 230000004913 activation Effects 0.000 claims description 39
• 230000000694 effects Effects 0.000 claims description 39
• 150000001413 amino acids Chemical class 0.000 claims description 35
• 238000002493 microarray Methods 0.000 claims description 28
• 239000012634 fragment Substances 0.000 claims description 25
• 239000002246 antineoplastic agent Substances 0.000 claims description 24
• 208000026310 Breast neoplasm Diseases 0.000 claims description 22
• 108060001084 Luciferase Proteins 0.000 claims description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims description 22
• 239000005089 Luciferase Substances 0.000 claims description 21
• 102000047766 human LGR5 Human genes 0.000 claims description 19
• 229940127089 cytotoxic agent Drugs 0.000 claims description 18
• 238000000338 in vitro Methods 0.000 claims description 17
• 101000825960 Homo sapiens R-spondin-3 Proteins 0.000 claims description 15
• 101000825962 Homo sapiens R-spondin-4 Proteins 0.000 claims description 15
• 238000002560 therapeutic procedure Methods 0.000 claims description 15
• 101000825949 Homo sapiens R-spondin-2 Proteins 0.000 claims description 14
• 102100022766 R-spondin-3 Human genes 0.000 claims description 14
• 102100022759 R-spondin-4 Human genes 0.000 claims description 14
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 13
• 102100022763 R-spondin-2 Human genes 0.000 claims description 13
• 229960000684 cytarabine Drugs 0.000 claims description 13
• 108020001507 fusion proteins Proteins 0.000 claims description 11
• 102000037865 fusion proteins Human genes 0.000 claims description 11
• 208000020816 lung neoplasm Diseases 0.000 claims description 11
• 210000004901 leucine-rich repeat Anatomy 0.000 claims description 9
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 8
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 8
• 229960002949 fluorouracil Drugs 0.000 claims description 7
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 6
• 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 claims description 6
• 210000004072 lung Anatomy 0.000 claims description 6
• 229960000485 methotrexate Drugs 0.000 claims description 6
• 229960004857 mitomycin Drugs 0.000 claims description 5
• IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 4
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 4
• 210000000481 breast Anatomy 0.000 claims description 4
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 4
• 229960004630 chlorambucil Drugs 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 4
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 4
• 229960001924 melphalan Drugs 0.000 claims description 4
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 4
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 4
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 3
• 102000003839 Human Proteins Human genes 0.000 claims description 3
• 108090000144 Human Proteins Proteins 0.000 claims description 3
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 3
• 229960000975 daunorubicin Drugs 0.000 claims description 3
• 229960004679 doxorubicin Drugs 0.000 claims description 3
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 3
• 229960005420 etoposide Drugs 0.000 claims description 3
• 108010006654 Bleomycin Proteins 0.000 claims description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
• 108010092160 Dactinomycin Proteins 0.000 claims description 2
• 229930192392 Mitomycin Natural products 0.000 claims description 2
• 229930012538 Paclitaxel Natural products 0.000 claims description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 2
• 229960001561 bleomycin Drugs 0.000 claims description 2
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
• 229960004316 cisplatin Drugs 0.000 claims description 2
• 229960001338 colchicine Drugs 0.000 claims description 2
• 229960004397 cyclophosphamide Drugs 0.000 claims description 2
• 229960000640 dactinomycin Drugs 0.000 claims description 2
• RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 claims description 2
• 229960000961 floxuridine Drugs 0.000 claims description 2
• 229960004768 irinotecan Drugs 0.000 claims description 2
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 2
• 229960001428 mercaptopurine Drugs 0.000 claims description 2
• 229960001592 paclitaxel Drugs 0.000 claims description 2
• 210000000496 pancreas Anatomy 0.000 claims description 2
• 210000002307 prostate Anatomy 0.000 claims description 2
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 2
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 2
• 229960001278 teniposide Drugs 0.000 claims description 2
• 229960003087 tioguanine Drugs 0.000 claims description 2
• 229960003048 vinblastine Drugs 0.000 claims description 2
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 2
• 229960004528 vincristine Drugs 0.000 claims description 2
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 2
• 230000003211 malignant effect Effects 0.000 claims 3
• 241000219198 Brassica Species 0.000 claims 1
• 235000003351 Brassica cretica Nutrition 0.000 claims 1
• 235000003343 Brassica rupestris Nutrition 0.000 claims 1
• QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 claims 1
• 201000006385 lung benign neoplasm Diseases 0.000 claims 1
• 235000010460 mustard Nutrition 0.000 claims 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 abstract description 3
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 abstract description 3
• 210000000130 stem cell Anatomy 0.000 description 197
• 235000018102 proteins Nutrition 0.000 description 192
• 150000001875 compounds Chemical class 0.000 description 66
• 239000000439 tumor marker Substances 0.000 description 56
• 239000003814 drug Substances 0.000 description 52
• 210000001519 tissue Anatomy 0.000 description 46
• 241001465754 Metazoa Species 0.000 description 44
• 238000012360 testing method Methods 0.000 description 42
• 108090000765 processed proteins & peptides Proteins 0.000 description 41
• 239000000523 sample Substances 0.000 description 40
• 108020004999 messenger RNA Proteins 0.000 description 39
• 238000003556 assay Methods 0.000 description 38
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 37
• 235000001014 amino acid Nutrition 0.000 description 36
• 239000003550 marker Substances 0.000 description 36
• 229940124597 therapeutic agent Drugs 0.000 description 36
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 35
• 150000007523 nucleic acids Chemical group 0.000 description 35
• 102000004196 processed proteins & peptides Human genes 0.000 description 34
• 229920001184 polypeptide Polymers 0.000 description 31
• 230000004614 tumor growth Effects 0.000 description 31
• 206010009944 Colon cancer Diseases 0.000 description 27
• 102000039446 nucleic acids Human genes 0.000 description 27
• 108020004707 nucleic acids Proteins 0.000 description 27
• 108020004414 DNA Proteins 0.000 description 26
• 201000010099 disease Diseases 0.000 description 25
• 102000040430 polynucleotide Human genes 0.000 description 25
• 108091033319 polynucleotide Proteins 0.000 description 25
• 239000002157 polynucleotide Substances 0.000 description 25
• 238000001727 in vivo Methods 0.000 description 24
• 230000003993 interaction Effects 0.000 description 24
• 238000001514 detection method Methods 0.000 description 23
• 238000004519 manufacturing process Methods 0.000 description 21
• 230000000381 tumorigenic effect Effects 0.000 description 21
• 239000002299 complementary DNA Substances 0.000 description 20
• 238000012216 screening Methods 0.000 description 20
• 231100000588 tumorigenic Toxicity 0.000 description 20
• 206010006187 Breast cancer Diseases 0.000 description 19
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 19
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 19
• 238000004458 analytical method Methods 0.000 description 19
• 239000002771 cell marker Substances 0.000 description 19
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 19
• 238000012546 transfer Methods 0.000 description 19
• 108091028043 Nucleic acid sequence Proteins 0.000 description 18
• 108700019146 Transgenes Proteins 0.000 description 18
• -1 rRNA Proteins 0.000 description 18
• 230000015572 biosynthetic process Effects 0.000 description 17
• 239000000306 component Substances 0.000 description 17
• 238000009396 hybridization Methods 0.000 description 17
• 239000002773 nucleotide Substances 0.000 description 17
• 125000003729 nucleotide group Chemical group 0.000 description 17
• 206010027476 Metastases Diseases 0.000 description 16
• 241000699666 Mus <mouse, genus> Species 0.000 description 16
• 108091034117 Oligonucleotide Proteins 0.000 description 16
• 238000001574 biopsy Methods 0.000 description 16
• 210000004408 hybridoma Anatomy 0.000 description 16
• 108020004459 Small interfering RNA Proteins 0.000 description 15
• 231100001221 nontumorigenic Toxicity 0.000 description 15
• 239000000047 product Substances 0.000 description 15
• 108091026890 Coding region Proteins 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 14
• 229940079593 drug Drugs 0.000 description 14
• 230000009401 metastasis Effects 0.000 description 14
• 230000035772 mutation Effects 0.000 description 14
• 239000012071 phase Substances 0.000 description 14
• 238000002965 ELISA Methods 0.000 description 13
• 108700013515 Wnt3A Proteins 0.000 description 13
• 102000044880 Wnt3A Human genes 0.000 description 13
• 230000005764 inhibitory process Effects 0.000 description 13
• 238000002474 experimental method Methods 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• 230000001225 therapeutic effect Effects 0.000 description 12
• 102000013814 Wnt Human genes 0.000 description 11
• 108050003627 Wnt Proteins 0.000 description 11
• 230000000890 antigenic effect Effects 0.000 description 11
• 230000000295 complement effect Effects 0.000 description 11
• 239000013604 expression vector Substances 0.000 description 11
• 238000003018 immunoassay Methods 0.000 description 11
• 239000000758 substrate Substances 0.000 description 11
• 230000009261 transgenic effect Effects 0.000 description 11
• 125000003275 alpha amino acid group Chemical group 0.000 description 10
• 239000003153 chemical reaction reagent Substances 0.000 description 10
• 208000035475 disorder Diseases 0.000 description 10
• 230000002068 genetic effect Effects 0.000 description 10
• 230000002829 reductive effect Effects 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• 239000003053 toxin Substances 0.000 description 10
• 231100000765 toxin Toxicity 0.000 description 10
• 108700012359 toxins Proteins 0.000 description 10
• 239000013598 vector Substances 0.000 description 10
• 108020004635 Complementary DNA Proteins 0.000 description 9
• 108020004511 Recombinant DNA Proteins 0.000 description 9
• 230000007423 decrease Effects 0.000 description 9
• 238000011161 development Methods 0.000 description 9
• 239000000975 dye Substances 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• 239000000499 gel Substances 0.000 description 9
• 241000894007 species Species 0.000 description 9
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 8
• 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 8
• 108091092195 Intron Proteins 0.000 description 8
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 8
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 8
• 230000004075 alteration Effects 0.000 description 8
• 230000000692 anti-sense effect Effects 0.000 description 8
• 230000003247 decreasing effect Effects 0.000 description 8
• 230000002255 enzymatic effect Effects 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• 238000011534 incubation Methods 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 201000005202 lung cancer Diseases 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 238000004393 prognosis Methods 0.000 description 8
• 230000001105 regulatory effect Effects 0.000 description 8
• 230000004044 response Effects 0.000 description 8
• 230000001177 retroviral effect Effects 0.000 description 8
• 238000012340 reverse transcriptase PCR Methods 0.000 description 8
• 210000002966 serum Anatomy 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• 238000001890 transfection Methods 0.000 description 8
• 102100032912 CD44 antigen Human genes 0.000 description 7
• 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 7
• 239000004698 Polyethylene Substances 0.000 description 7
• 241000700605 Viruses Species 0.000 description 7
• 238000010171 animal model Methods 0.000 description 7
• 239000008280 blood Substances 0.000 description 7
• 238000004590 computer program Methods 0.000 description 7
• 238000007796 conventional method Methods 0.000 description 7
• 231100000599 cytotoxic agent Toxicity 0.000 description 7
• 238000005516 engineering process Methods 0.000 description 7
• 238000000684 flow cytometry Methods 0.000 description 7
• 230000003053 immunization Effects 0.000 description 7
• 230000006698 induction Effects 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 238000002372 labelling Methods 0.000 description 7
• 239000002609 medium Substances 0.000 description 7
• 230000035755 proliferation Effects 0.000 description 7
• 241000699670 Mus sp. Species 0.000 description 6
• 206010060862 Prostate cancer Diseases 0.000 description 6
• 210000004369 blood Anatomy 0.000 description 6
• 230000032823 cell division Effects 0.000 description 6
• 210000000349 chromosome Anatomy 0.000 description 6
• 210000001072 colon Anatomy 0.000 description 6
• 238000012875 competitive assay Methods 0.000 description 6
• 239000002254 cytotoxic agent Substances 0.000 description 6
• 230000034994 death Effects 0.000 description 6
• 231100000517 death Toxicity 0.000 description 6
• 239000003446 ligand Substances 0.000 description 6
• 230000000670 limiting effect Effects 0.000 description 6
• 210000001161 mammalian embryo Anatomy 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• 238000012545 processing Methods 0.000 description 6
• 230000002062 proliferating effect Effects 0.000 description 6
• 238000003127 radioimmunoassay Methods 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 239000000243 solution Substances 0.000 description 6
• 238000006467 substitution reaction Methods 0.000 description 6
• 230000004083 survival effect Effects 0.000 description 6
• 230000002195 synergetic effect Effects 0.000 description 6
• 238000001262 western blot Methods 0.000 description 6
• 241000196324 Embryophyta Species 0.000 description 5
• 241000238631 Hexapoda Species 0.000 description 5
• 239000011324 bead Substances 0.000 description 5
• 230000033228 biological regulation Effects 0.000 description 5
• 230000001413 cellular effect Effects 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 230000021615 conjugation Effects 0.000 description 5
• 239000003623 enhancer Substances 0.000 description 5
• 238000002649 immunization Methods 0.000 description 5
• 238000010166 immunofluorescence Methods 0.000 description 5
• 229940055742 indium-111 Drugs 0.000 description 5
• APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 5
• 239000003112 inhibitor Substances 0.000 description 5
• 210000004698 lymphocyte Anatomy 0.000 description 5
• 238000012423 maintenance Methods 0.000 description 5
• 239000011159 matrix material Substances 0.000 description 5
• 206010061289 metastatic neoplasm Diseases 0.000 description 5
• 238000010208 microarray analysis Methods 0.000 description 5
• 238000000520 microinjection Methods 0.000 description 5
• 239000013610 patient sample Substances 0.000 description 5
• 239000013641 positive control Substances 0.000 description 5
• 239000013615 primer Substances 0.000 description 5
• 238000001959 radiotherapy Methods 0.000 description 5
• 230000008685 targeting Effects 0.000 description 5
• 238000013518 transcription Methods 0.000 description 5
• 230000035897 transcription Effects 0.000 description 5
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
• 239000012981 Hank's balanced salt solution Substances 0.000 description 4
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 4
• 101001039199 Homo sapiens Low-density lipoprotein receptor-related protein 6 Proteins 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• 241001529936 Murinae Species 0.000 description 4
• 239000000020 Nitrocellulose Substances 0.000 description 4
• 238000000636 Northern blotting Methods 0.000 description 4
• 239000004677 Nylon Substances 0.000 description 4
• 241000283973 Oryctolagus cuniculus Species 0.000 description 4
• GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 4
• 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 4
• 239000002253 acid Substances 0.000 description 4
• 238000007792 addition Methods 0.000 description 4
• 230000001093 anti-cancer Effects 0.000 description 4
• 230000000259 anti-tumor effect Effects 0.000 description 4
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 239000012472 biological sample Substances 0.000 description 4
• 210000004952 blastocoel Anatomy 0.000 description 4
• 210000000988 bone and bone Anatomy 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 231100000504 carcinogenesis Toxicity 0.000 description 4
• 238000002512 chemotherapy Methods 0.000 description 4
• 239000006185 dispersion Substances 0.000 description 4
• 230000003828 downregulation Effects 0.000 description 4
• 238000001962 electrophoresis Methods 0.000 description 4
• 239000012530 fluid Substances 0.000 description 4
• 230000009368 gene silencing by RNA Effects 0.000 description 4
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
• 229960002897 heparin Drugs 0.000 description 4
• 229920000669 heparin Polymers 0.000 description 4
• 238000001794 hormone therapy Methods 0.000 description 4
• 102000049181 human LGR4 Human genes 0.000 description 4
• 102000050526 human RSPO1 Human genes 0.000 description 4
• 230000028993 immune response Effects 0.000 description 4
• 229940072221 immunoglobulins Drugs 0.000 description 4
• 238000000099 in vitro assay Methods 0.000 description 4
• 238000011503 in vivo imaging Methods 0.000 description 4
• 208000015181 infectious disease Diseases 0.000 description 4
• 210000004185 liver Anatomy 0.000 description 4
• 210000001165 lymph node Anatomy 0.000 description 4
• 230000001394 metastastic effect Effects 0.000 description 4
• 229920001220 nitrocellulos Polymers 0.000 description 4
• 229920001778 nylon Polymers 0.000 description 4
• 238000011275 oncology therapy Methods 0.000 description 4
• 210000000056 organ Anatomy 0.000 description 4
• 239000013612 plasmid Substances 0.000 description 4
• 230000008488 polyadenylation Effects 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 230000002285 radioactive effect Effects 0.000 description 4
• 150000003384 small molecules Chemical class 0.000 description 4
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 229940056501 technetium 99m Drugs 0.000 description 4
• 238000013519 translation Methods 0.000 description 4
• 241000701447 unidentified baculovirus Species 0.000 description 4
• 241001430294 unidentified retrovirus Species 0.000 description 4
• 230000003827 upregulation Effects 0.000 description 4
• 241000894006 Bacteria Species 0.000 description 3
• 102000053602 DNA Human genes 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 108091006020 Fc-tagged proteins Proteins 0.000 description 3
• 102100021261 Frizzled-10 Human genes 0.000 description 3
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 3
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 3
• GYHNNYVSQQEPJS-OIOBTWANSA-N Gallium-67 Chemical compound [67Ga] GYHNNYVSQQEPJS-OIOBTWANSA-N 0.000 description 3
• 101000819451 Homo sapiens Frizzled-10 Proteins 0.000 description 3
• 206010061598 Immunodeficiency Diseases 0.000 description 3
• QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 3
• 108010043958 Peptoids Proteins 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 238000001042 affinity chromatography Methods 0.000 description 3
• 238000007818 agglutination assay Methods 0.000 description 3
• 125000000539 amino acid group Chemical group 0.000 description 3
• 229940041181 antineoplastic drug Drugs 0.000 description 3
• 230000017047 asymmetric cell division Effects 0.000 description 3
• 230000001588 bifunctional effect Effects 0.000 description 3
• 210000001109 blastomere Anatomy 0.000 description 3
• 210000001124 body fluid Anatomy 0.000 description 3
• 239000010839 body fluid Substances 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 239000002738 chelating agent Substances 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• 238000003776 cleavage reaction Methods 0.000 description 3
• 238000004891 communication Methods 0.000 description 3
• 230000002860 competitive effect Effects 0.000 description 3
• 239000000356 contaminant Substances 0.000 description 3
• 231100000433 cytotoxic Toxicity 0.000 description 3
• 230000001472 cytotoxic effect Effects 0.000 description 3
• 238000012217 deletion Methods 0.000 description 3
• 230000037430 deletion Effects 0.000 description 3
• 238000004925 denaturation Methods 0.000 description 3
• 230000036425 denaturation Effects 0.000 description 3
• 238000002405 diagnostic procedure Methods 0.000 description 3
• 239000010432 diamond Substances 0.000 description 3
• 238000010494 dissociation reaction Methods 0.000 description 3
• 230000005593 dissociations Effects 0.000 description 3
• 230000008030 elimination Effects 0.000 description 3
• 238000003379 elimination reaction Methods 0.000 description 3
• 210000002257 embryonic structure Anatomy 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 230000007613 environmental effect Effects 0.000 description 3
• 229940088598 enzyme Drugs 0.000 description 3
• 102000015694 estrogen receptors Human genes 0.000 description 3
• 108010038795 estrogen receptors Proteins 0.000 description 3
• 239000007850 fluorescent dye Substances 0.000 description 3
• 229940006110 gallium-67 Drugs 0.000 description 3
• 210000004602 germ cell Anatomy 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 210000003128 head Anatomy 0.000 description 3
• 201000010536 head and neck cancer Diseases 0.000 description 3
• 208000014829 head and neck neoplasm Diseases 0.000 description 3
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
• 102000054545 human LGR6 Human genes 0.000 description 3
• 238000003364 immunohistochemistry Methods 0.000 description 3
• 238000001114 immunoprecipitation Methods 0.000 description 3
• 230000006872 improvement Effects 0.000 description 3
• 238000005462 in vivo assay Methods 0.000 description 3
• 239000002502 liposome Substances 0.000 description 3
• 208000014018 liver neoplasm Diseases 0.000 description 3
• 230000005291 magnetic effect Effects 0.000 description 3
• 238000002595 magnetic resonance imaging Methods 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 201000000050 myeloid neoplasm Diseases 0.000 description 3
• 230000002914 neoplasic effect Effects 0.000 description 3
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
• 230000001575 pathological effect Effects 0.000 description 3
• 230000007170 pathology Effects 0.000 description 3
• 230000035515 penetration Effects 0.000 description 3
• 229960003330 pentetic acid Drugs 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 238000002600 positron emission tomography Methods 0.000 description 3
• 239000002243 precursor Substances 0.000 description 3
• 230000006798 recombination Effects 0.000 description 3
• 238000005215 recombination Methods 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 150000003839 salts Chemical class 0.000 description 3
• 230000007017 scission Effects 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 230000019491 signal transduction Effects 0.000 description 3
• 239000007790 solid phase Substances 0.000 description 3
• 206010041823 squamous cell carcinoma Diseases 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 238000013456 study Methods 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• 239000002562 thickening agent Substances 0.000 description 3
• 238000002054 transplantation Methods 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• HPZMWTNATZPBIH-UHFFFAOYSA-N 1-methyladenine Chemical compound CN1C=NC2=NC=NC2=C1N HPZMWTNATZPBIH-UHFFFAOYSA-N 0.000 description 2
• RFLVMTUMFYRZCB-UHFFFAOYSA-N 1-methylguanine Chemical compound O=C1N(C)C(N)=NC2=C1N=CN2 RFLVMTUMFYRZCB-UHFFFAOYSA-N 0.000 description 2
• PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 2
• YSAJFXWTVFGPAX-UHFFFAOYSA-N 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetic acid Chemical compound OC(=O)COC1=CNC(=O)NC1=O YSAJFXWTVFGPAX-UHFFFAOYSA-N 0.000 description 2
• WYMDDFRYORANCC-UHFFFAOYSA-N 2-[[3-[bis(carboxymethyl)amino]-2-hydroxypropyl]-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)CN(CC(O)=O)CC(O)=O WYMDDFRYORANCC-UHFFFAOYSA-N 0.000 description 2
• FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
• OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 2
• OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
• DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 2
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
• 229920000936 Agarose Polymers 0.000 description 2
• 108090000020 Alpha-catenin Proteins 0.000 description 2
• 102000003730 Alpha-catenin Human genes 0.000 description 2
• 101000669426 Aspergillus restrictus Ribonuclease mitogillin Proteins 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 206010055113 Breast cancer metastatic Diseases 0.000 description 2
• 208000005623 Carcinogenesis Diseases 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 102100035294 Chemokine XC receptor 1 Human genes 0.000 description 2
• 102000029816 Collagenase Human genes 0.000 description 2
• 108060005980 Collagenase Proteins 0.000 description 2
• 241000699800 Cricetinae Species 0.000 description 2
• 239000004971 Cross linker Substances 0.000 description 2
• 239000003155 DNA primer Substances 0.000 description 2
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
• 229920002307 Dextran Polymers 0.000 description 2
• 108010053187 Diphtheria Toxin Proteins 0.000 description 2
• 102000016607 Diphtheria Toxin Human genes 0.000 description 2
• 241000588724 Escherichia coli Species 0.000 description 2
• 201000006107 Familial adenomatous polyposis Diseases 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• 102100028466 Frizzled-8 Human genes 0.000 description 2
• GYHNNYVSQQEPJS-YPZZEJLDSA-N Gallium-68 Chemical compound [68Ga] GYHNNYVSQQEPJS-YPZZEJLDSA-N 0.000 description 2
• 108010024636 Glutathione Proteins 0.000 description 2
• 108010070675 Glutathione transferase Proteins 0.000 description 2
• 102000005720 Glutathione transferase Human genes 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000804783 Homo sapiens Chemokine XC receptor 1 Proteins 0.000 description 2
• 101001061408 Homo sapiens Frizzled-8 Proteins 0.000 description 2
• 238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 2
• 102100034343 Integrase Human genes 0.000 description 2
• 102100040704 Low-density lipoprotein receptor-related protein 6 Human genes 0.000 description 2
• 101100208721 Mus musculus Usp5 gene Proteins 0.000 description 2
• HYVABZIGRDEKCD-UHFFFAOYSA-N N(6)-dimethylallyladenine Chemical compound CC(C)=CCNC1=NC=NC2=C1N=CN2 HYVABZIGRDEKCD-UHFFFAOYSA-N 0.000 description 2
• 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
• 238000012408 PCR amplification Methods 0.000 description 2
• 208000002151 Pleural effusion Diseases 0.000 description 2
• 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
• 108091030071 RNAI Proteins 0.000 description 2
• 206010038997 Retroviral infections Diseases 0.000 description 2
• 108010039491 Ricin Proteins 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• 238000011579 SCID mouse model Methods 0.000 description 2
• 108091081021 Sense strand Proteins 0.000 description 2
• 108020004688 Small Nuclear RNA Proteins 0.000 description 2
• 102000039471 Small Nuclear RNA Human genes 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 238000002105 Southern blotting Methods 0.000 description 2
• 108010090804 Streptavidin Proteins 0.000 description 2
• 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 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 239000012190 activator Substances 0.000 description 2
• 230000003321 amplification Effects 0.000 description 2
• 239000003098 androgen Substances 0.000 description 2
• 230000002022 anti-cellular effect Effects 0.000 description 2
• 238000003491 array Methods 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 210000002459 blastocyst Anatomy 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 238000004159 blood analysis Methods 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 244000309466 calf Species 0.000 description 2
• 230000036952 cancer formation Effects 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 238000000423 cell based assay Methods 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 239000013592 cell lysate Substances 0.000 description 2
• 239000002458 cell surface marker Substances 0.000 description 2
• 230000000739 chaotic effect Effects 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 2
• 229960002424 collagenase Drugs 0.000 description 2
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
• 230000001143 conditioned effect Effects 0.000 description 2
• 239000013068 control sample Substances 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 238000012258 culturing Methods 0.000 description 2
• 238000007405 data analysis Methods 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 230000003292 diminished effect Effects 0.000 description 2
• 238000007877 drug screening Methods 0.000 description 2
• 239000012636 effector Substances 0.000 description 2
• 235000013601 eggs Nutrition 0.000 description 2
• 210000002308 embryonic cell Anatomy 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 210000002889 endothelial cell Anatomy 0.000 description 2
• 239000002158 endotoxin Substances 0.000 description 2
• 230000006862 enzymatic digestion Effects 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 238000001502 gel electrophoresis Methods 0.000 description 2
• 238000012817 gel-diffusion technique Methods 0.000 description 2
• 230000030279 gene silencing Effects 0.000 description 2
• 238000010353 genetic engineering Methods 0.000 description 2
• 229960003180 glutathione Drugs 0.000 description 2
• 229910052737 gold Inorganic materials 0.000 description 2
• 239000010931 gold Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 208000013210 hematogenous Diseases 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 238000002744 homologous recombination Methods 0.000 description 2
• 230000006801 homologous recombination Effects 0.000 description 2
• 102000055436 human LRP6 Human genes 0.000 description 2
• 238000003384 imaging method Methods 0.000 description 2
• 229940127121 immunoconjugate Drugs 0.000 description 2
• 230000000951 immunodiffusion Effects 0.000 description 2
• 239000002596 immunotoxin Substances 0.000 description 2
• 230000002637 immunotoxin Effects 0.000 description 2
• 229940051026 immunotoxin Drugs 0.000 description 2
• 231100000608 immunotoxin Toxicity 0.000 description 2
• 230000008595 infiltration Effects 0.000 description 2
• 238000001764 infiltration Methods 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 230000000968 intestinal effect Effects 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 239000007928 intraperitoneal injection Substances 0.000 description 2
• 238000007913 intrathecal administration Methods 0.000 description 2
• 238000007914 intraventricular administration Methods 0.000 description 2
• 238000004255 ion exchange chromatography Methods 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 238000005304 joining Methods 0.000 description 2
• 210000000867 larynx Anatomy 0.000 description 2
• 230000002045 lasting effect Effects 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 201000007270 liver cancer Diseases 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 210000004379 membrane Anatomy 0.000 description 2
• 208000037819 metastatic cancer Diseases 0.000 description 2
• 208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
• 210000000214 mouth Anatomy 0.000 description 2
• 238000002703 mutagenesis Methods 0.000 description 2
• 231100000350 mutagenesis Toxicity 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 238000007899 nucleic acid hybridization Methods 0.000 description 2
• 210000000287 oocyte Anatomy 0.000 description 2
• 230000008520 organization Effects 0.000 description 2
• 210000003300 oropharynx Anatomy 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• 230000005298 paramagnetic effect Effects 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 238000002823 phage display Methods 0.000 description 2
• 239000002831 pharmacologic agent Substances 0.000 description 2
• 239000013600 plasmid vector Substances 0.000 description 2
• 208000015768 polyposis Diseases 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 210000000664 rectum Anatomy 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 238000010839 reverse transcription Methods 0.000 description 2
• 238000007423 screening assay Methods 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 229910001415 sodium ion Inorganic materials 0.000 description 2
• 210000004872 soft tissue Anatomy 0.000 description 2
• 230000004936 stimulating effect Effects 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000007929 subcutaneous injection Substances 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
• 238000004448 titration Methods 0.000 description 2
• 230000004565 tumor cell growth Effects 0.000 description 2
• 210000002700 urine Anatomy 0.000 description 2
• 210000005166 vasculature Anatomy 0.000 description 2
• 230000035899 viability Effects 0.000 description 2
• NNJPGOLRFBJNIW-HNNXBMFYSA-N (-)-demecolcine Chemical compound C1=C(OC)C(=O)C=C2[C@@H](NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-HNNXBMFYSA-N 0.000 description 1
• YMXHPSHLTSZXKH-RVBZMBCESA-N (2,5-dioxopyrrolidin-1-yl) 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)ON1C(=O)CCC1=O YMXHPSHLTSZXKH-RVBZMBCESA-N 0.000 description 1
• IEUUDEWWMRQUDS-UHFFFAOYSA-N (6-azaniumylidene-1,6-dimethoxyhexylidene)azanium;dichloride Chemical compound Cl.Cl.COC(=N)CCCCC(=N)OC IEUUDEWWMRQUDS-UHFFFAOYSA-N 0.000 description 1
• VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
• SATCOUWSAZBIJO-UHFFFAOYSA-N 1-methyladenine Natural products N=C1N(C)C=NC2=C1NC=N2 SATCOUWSAZBIJO-UHFFFAOYSA-N 0.000 description 1
• WJNGQIYEQLPJMN-IOSLPCCCSA-N 1-methylinosine Chemical compound C1=NC=2C(=O)N(C)C=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O WJNGQIYEQLPJMN-IOSLPCCCSA-N 0.000 description 1
• WUAPFZMCVAUBPE-NJFSPNSNSA-N 188Re Chemical compound [188Re] WUAPFZMCVAUBPE-NJFSPNSNSA-N 0.000 description 1
• YBBNVCVOACOHIG-UHFFFAOYSA-N 2,2-diamino-1,4-bis(4-azidophenyl)-3-butylbutane-1,4-dione Chemical compound C=1C=C(N=[N+]=[N-])C=CC=1C(=O)C(N)(N)C(CCCC)C(=O)C1=CC=C(N=[N+]=[N-])C=C1 YBBNVCVOACOHIG-UHFFFAOYSA-N 0.000 description 1
• HLYBTPMYFWWNJN-UHFFFAOYSA-N 2-(2,4-dioxo-1h-pyrimidin-5-yl)-2-hydroxyacetic acid Chemical compound OC(=O)C(O)C1=CNC(=O)NC1=O HLYBTPMYFWWNJN-UHFFFAOYSA-N 0.000 description 1
• SVBOROZXXYRWJL-UHFFFAOYSA-N 2-[(4-oxo-2-sulfanylidene-1h-pyrimidin-5-yl)methylamino]acetic acid Chemical compound OC(=O)CNCC1=CNC(=S)NC1=O SVBOROZXXYRWJL-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• RAZLJUXJEOEYAM-UHFFFAOYSA-N 2-[bis[2-(2,6-dioxomorpholin-4-yl)ethyl]azaniumyl]acetate Chemical compound C1C(=O)OC(=O)CN1CCN(CC(=O)O)CCN1CC(=O)OC(=O)C1 RAZLJUXJEOEYAM-UHFFFAOYSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• XMSMHKMPBNTBOD-UHFFFAOYSA-N 2-dimethylamino-6-hydroxypurine Chemical compound N1C(N(C)C)=NC(=O)C2=C1N=CN2 XMSMHKMPBNTBOD-UHFFFAOYSA-N 0.000 description 1
• SMADWRYCYBUIKH-UHFFFAOYSA-N 2-methyl-7h-purin-6-amine Chemical compound CC1=NC(N)=C2NC=NC2=N1 SMADWRYCYBUIKH-UHFFFAOYSA-N 0.000 description 1
• 108020005065 3' Flanking Region Proteins 0.000 description 1
• KOLPWZCZXAMXKS-UHFFFAOYSA-N 3-methylcytosine Chemical compound CN1C(N)=CC=NC1=O KOLPWZCZXAMXKS-UHFFFAOYSA-N 0.000 description 1
• GJAKJCICANKRFD-UHFFFAOYSA-N 4-acetyl-4-amino-1,3-dihydropyrimidin-2-one Chemical compound CC(=O)C1(N)NC(=O)NC=C1 GJAKJCICANKRFD-UHFFFAOYSA-N 0.000 description 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
• 108020005029 5' Flanking Region Proteins 0.000 description 1
• UACOJOVKHNAJPX-UHFFFAOYSA-N 5-(methoxyamino)-6-methyl-2-sulfanylidene-1H-pyrimidin-4-one Chemical compound CONC=1C(NC(NC=1C)=S)=O UACOJOVKHNAJPX-UHFFFAOYSA-N 0.000 description 1
• MQJSSLBGAQJNER-UHFFFAOYSA-N 5-(methylaminomethyl)-1h-pyrimidine-2,4-dione Chemical compound CNCC1=CNC(=O)NC1=O MQJSSLBGAQJNER-UHFFFAOYSA-N 0.000 description 1
• LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
• KELXHQACBIUYSE-UHFFFAOYSA-N 5-methoxy-1h-pyrimidine-2,4-dione Chemical compound COC1=CNC(=O)NC1=O KELXHQACBIUYSE-UHFFFAOYSA-N 0.000 description 1
• ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 description 1
• LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
• GTSVFOOLVUMMCX-UHFFFAOYSA-N 6-(methylaminomethyl)-2,4-dioxo-1H-pyrimidine-5-carboxylic acid Chemical compound C(=O)(O)C=1C(NC(NC=1CNC)=O)=O GTSVFOOLVUMMCX-UHFFFAOYSA-N 0.000 description 1
• CKOMXBHMKXXTNW-UHFFFAOYSA-N 6-methyladenine Chemical compound CNC1=NC=NC2=C1N=CN2 CKOMXBHMKXXTNW-UHFFFAOYSA-N 0.000 description 1
• VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
• SWJYOKZMYFJUOY-KQYNXXCUSA-N 9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(methylamino)-7h-purin-8-one Chemical compound OC1=NC=2C(NC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O SWJYOKZMYFJUOY-KQYNXXCUSA-N 0.000 description 1
• MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
• 108010066676 Abrin Proteins 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
• 241000701242 Adenoviridae Species 0.000 description 1
• 102100027211 Albumin Human genes 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 239000012099 Alexa Fluor family Substances 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 1
• 108020005544 Antisense RNA Proteins 0.000 description 1
• 108091023037 Aptamer Proteins 0.000 description 1
• 206010003445 Ascites Diseases 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 108010041884 CD4 Immunoadhesins Proteins 0.000 description 1
• 101100264195 Caenorhabditis elegans app-1 gene Proteins 0.000 description 1
• 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
• 101710158575 Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase Proteins 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 108010078791 Carrier Proteins Proteins 0.000 description 1
• 108090000994 Catalytic RNA Proteins 0.000 description 1
• 102000053642 Catalytic RNA Human genes 0.000 description 1
• 102000016362 Catenins Human genes 0.000 description 1
• 108010067316 Catenins Proteins 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 206010009192 Circulatory collapse Diseases 0.000 description 1
• 108091033380 Coding strand Proteins 0.000 description 1
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 230000006820 DNA synthesis Effects 0.000 description 1
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
• NNJPGOLRFBJNIW-UHFFFAOYSA-N Demecolcine Natural products C1=C(OC)C(=O)C=C2C(NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-UHFFFAOYSA-N 0.000 description 1
• 241000702421 Dependoparvovirus Species 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 241000283074 Equus asinus Species 0.000 description 1
• 108060002716 Exonuclease Proteins 0.000 description 1
• 101710082714 Exotoxin A Proteins 0.000 description 1
• 108010087819 Fc receptors Proteins 0.000 description 1
• 102000009109 Fc receptors Human genes 0.000 description 1
• 108010045438 Frizzled receptors Proteins 0.000 description 1
• 102000005698 Frizzled receptors Human genes 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 108700012941 GNRH1 Proteins 0.000 description 1
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
• 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
• 101000678026 Homo sapiens Alpha-1-antichymotrypsin Proteins 0.000 description 1
• 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
• 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
• 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
• 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
• 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
• 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
• 101001043594 Homo sapiens Low-density lipoprotein receptor-related protein 5 Proteins 0.000 description 1
• 206010062904 Hormone-refractory prostate cancer Diseases 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
• 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
• 229930010555 Inosine Natural products 0.000 description 1
• UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• 241000761557 Lamina Species 0.000 description 1
• 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
• 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
• 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
• 102100021926 Low-density lipoprotein receptor-related protein 5 Human genes 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
• 244000302512 Momordica charantia Species 0.000 description 1
• 235000009811 Momordica charantia Nutrition 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical compound O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
• 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
• 108020003217 Nuclear RNA Proteins 0.000 description 1
• 102000043141 Nuclear RNA Human genes 0.000 description 1
• 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
• 108700020796 Oncogene Proteins 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 241000237988 Patellidae Species 0.000 description 1
• 102000007079 Peptide Fragments Human genes 0.000 description 1
• 108010033276 Peptide Fragments Proteins 0.000 description 1
• 108010067902 Peptide Library Proteins 0.000 description 1
• 108010004729 Phycoerythrin Proteins 0.000 description 1
• 101100413173 Phytolacca americana PAP2 gene Proteins 0.000 description 1
• 241000276498 Pollachius virens Species 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 108010039918 Polylysine Proteins 0.000 description 1
• 108010076504 Protein Sorting Signals Proteins 0.000 description 1
• 241000589516 Pseudomonas Species 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 108700008625 Reporter Genes Proteins 0.000 description 1
• 108010083644 Ribonucleases Proteins 0.000 description 1
• 102000006382 Ribonucleases Human genes 0.000 description 1
• 108090000829 Ribosome Inactivating Proteins Proteins 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 206010061934 Salivary gland cancer Diseases 0.000 description 1
• 241000192023 Sarcina Species 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 108091008874 T cell receptors Proteins 0.000 description 1
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
• 238000012338 Therapeutic targeting Methods 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 101710120037 Toxin CcdB Proteins 0.000 description 1
• 102100040396 Transcobalamin-1 Human genes 0.000 description 1
• 101710124861 Transcobalamin-1 Proteins 0.000 description 1
• 206010054094 Tumour necrosis Diseases 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 240000001866 Vernicia fordii Species 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 1
• 241000863480 Vinca Species 0.000 description 1
• 108700005077 Viral Genes Proteins 0.000 description 1
• 206010047741 Vulval cancer Diseases 0.000 description 1
• 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
• 230000004156 Wnt signaling pathway Effects 0.000 description 1
• 108700020987 Wnt-1 Proteins 0.000 description 1
• 102000052547 Wnt-1 Human genes 0.000 description 1
• 241000021375 Xenogenes Species 0.000 description 1
• VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 description 1
• HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
• 238000002679 ablation Methods 0.000 description 1
• 230000002159 abnormal effect 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
• 229960004150 aciclovir Drugs 0.000 description 1
• MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 238000011374 additional therapy Methods 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 108700010877 adenoviridae proteins Proteins 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 210000004100 adrenal gland Anatomy 0.000 description 1
• 229940009456 adriamycin Drugs 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000011543 agarose gel Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229930013930 alkaloid Natural products 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229960003896 aminopterin Drugs 0.000 description 1
• 239000012491 analyte Substances 0.000 description 1
• 230000001548 androgenic effect Effects 0.000 description 1
• 229940030486 androgens Drugs 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 230000002547 anomalous effect Effects 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000006023 anti-tumor response Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 230000009833 antibody interaction Effects 0.000 description 1
• 229940037157 anticorticosteroids Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000000074 antisense oligonucleotide Substances 0.000 description 1
• 238000012230 antisense oligonucleotides Methods 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 150000008209 arabinosides Chemical class 0.000 description 1
• XKRFYHLGVUSROY-UHFFFAOYSA-N argon Substances [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 239000003886 aromatase inhibitor Substances 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• FIVPIPIDMRVLAY-UHFFFAOYSA-N aspergillin Natural products C1C2=CC=CC(O)C2N2C1(SS1)C(=O)N(C)C1(CO)C2=O FIVPIPIDMRVLAY-UHFFFAOYSA-N 0.000 description 1
• 239000003212 astringent agent Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 208000025261 autosomal dominant disease Diseases 0.000 description 1
• 239000012752 auxiliary agent Substances 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 230000000975 bioactive effect Effects 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 230000008236 biological pathway Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 238000005460 biophysical method Methods 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 238000007413 biotinylation Methods 0.000 description 1
• 230000006287 biotinylation Effects 0.000 description 1
• 201000000053 blastoma Diseases 0.000 description 1
• 239000010836 blood and blood product Substances 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 239000012503 blood component Substances 0.000 description 1
• 229940125691 blood product Drugs 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 229930195731 calicheamicin Natural products 0.000 description 1
• HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000004700 cellular uptake Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 230000009920 chelation Effects 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 238000002038 chemiluminescence detection Methods 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• 238000009104 chemotherapy regimen Methods 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 238000000975 co-precipitation Methods 0.000 description 1
• 239000000701 coagulant Substances 0.000 description 1
• 201000010989 colorectal carcinoma Diseases 0.000 description 1
• 230000009137 competitive binding Effects 0.000 description 1
• 239000003184 complementary RNA Substances 0.000 description 1
• 238000002591 computed tomography Methods 0.000 description 1
• 239000003636 conditioned culture medium Substances 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 239000012059 conventional drug carrier Substances 0.000 description 1
• RYGMFSIKBFXOCR-AKLPVKDBSA-N copper-67 Chemical compound [67Cu] RYGMFSIKBFXOCR-AKLPVKDBSA-N 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000009109 curative therapy Methods 0.000 description 1
• 238000011461 current therapy Methods 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 238000004163 cytometry Methods 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 229940104302 cytosine Drugs 0.000 description 1
• 239000002619 cytotoxin Substances 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 230000002498 deadly effect Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 229960005052 demecolcine Drugs 0.000 description 1
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
• 239000005547 deoxyribonucleotide Substances 0.000 description 1
• 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000000368 destabilizing effect Effects 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 238000001085 differential centrifugation Methods 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 125000005442 diisocyanate group Chemical group 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 206010013023 diphtheria Diseases 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000007878 drug screening assay Methods 0.000 description 1
• 238000002565 electrocardiography Methods 0.000 description 1
• 201000008184 embryoma Diseases 0.000 description 1
• 210000001671 embryonic stem cell Anatomy 0.000 description 1
• 201000003914 endometrial carcinoma Diseases 0.000 description 1
• 230000002357 endometrial effect Effects 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 108010028531 enomycin Proteins 0.000 description 1
• 239000005447 environmental material Substances 0.000 description 1
• 230000007515 enzymatic degradation Effects 0.000 description 1
• 208000037828 epithelial carcinoma Diseases 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 102000013165 exonuclease Human genes 0.000 description 1
• 238000010195 expression analysis Methods 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 238000001917 fluorescence detection Methods 0.000 description 1
• 150000002222 fluorine compounds Chemical class 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
• 235000008191 folinic acid Nutrition 0.000 description 1
• 239000011672 folinic acid Substances 0.000 description 1
• 230000005714 functional activity Effects 0.000 description 1
• 230000002538 fungal effect Effects 0.000 description 1
• RJOJUSXNYCILHH-UHFFFAOYSA-N gadolinium(3+) Chemical compound [Gd+3] RJOJUSXNYCILHH-UHFFFAOYSA-N 0.000 description 1
• 229960002963 ganciclovir Drugs 0.000 description 1
• IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 230000004547 gene signature Effects 0.000 description 1
• 238000012226 gene silencing method Methods 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• FIVPIPIDMRVLAY-RBJBARPLSA-N gliotoxin Chemical compound C1C2=CC=C[C@H](O)[C@H]2N2[C@]1(SS1)C(=O)N(C)[C@@]1(CO)C2=O FIVPIPIDMRVLAY-RBJBARPLSA-N 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 230000035931 haemagglutination Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 201000005787 hematologic cancer Diseases 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• 210000000777 hematopoietic system Anatomy 0.000 description 1
• 108060003552 hemocyanin Proteins 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 238000007417 hierarchical cluster analysis Methods 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 102000048851 human CD44 Human genes 0.000 description 1
• 102000054144 human RSPO3 Human genes 0.000 description 1
• 102000048108 human RSPO4 Human genes 0.000 description 1
• 102000047209 human Rspo2 Human genes 0.000 description 1
• 210000003026 hypopharynx Anatomy 0.000 description 1
• 150000002463 imidates Chemical class 0.000 description 1
• 230000003100 immobilizing effect Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 238000003119 immunoblot Methods 0.000 description 1
• 238000000760 immunoelectrophoresis Methods 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 230000016784 immunoglobulin production Effects 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 229910052738 indium Inorganic materials 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229960003786 inosine Drugs 0.000 description 1
• 239000012194 insect media Substances 0.000 description 1
• 238000009434 installation Methods 0.000 description 1
• 238000012482 interaction analysis Methods 0.000 description 1
• 239000000138 intercalating agent Substances 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• XMBWDFGMSWQBCA-YPZZEJLDSA-N iodane Chemical compound [125IH] XMBWDFGMSWQBCA-YPZZEJLDSA-N 0.000 description 1
• 229940044173 iodine-125 Drugs 0.000 description 1
• 239000003350 kerosene Substances 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 208000003849 large cell carcinoma Diseases 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 229960001691 leucovorin Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 210000000265 leukocyte Anatomy 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
• 150000002632 lipids Chemical class 0.000 description 1
• 238000001638 lipofection Methods 0.000 description 1
• 239000007791 liquid phase Substances 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 229960005015 local anesthetics Drugs 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
• 201000005249 lung adenocarcinoma Diseases 0.000 description 1
• 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 230000001926 lymphatic effect Effects 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 238000009115 maintenance therapy Methods 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 238000009607 mammography Methods 0.000 description 1
• 210000003519 mature b lymphocyte Anatomy 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 239000002923 metal particle Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
• IZAGSTRIDUNNOY-UHFFFAOYSA-N methyl 2-[(2,4-dioxo-1h-pyrimidin-5-yl)oxy]acetate Chemical compound COC(=O)COC1=CNC(=O)NC1=O IZAGSTRIDUNNOY-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 238000012775 microarray technology Methods 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 229910052651 microcline Inorganic materials 0.000 description 1
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)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](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](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 230000000877 morphologic effect Effects 0.000 description 1
• 108700039855 mouse a Proteins 0.000 description 1
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
• 210000004400 mucous membrane Anatomy 0.000 description 1
• 210000003097 mucus Anatomy 0.000 description 1
• XJVXMWNLQRTRGH-UHFFFAOYSA-N n-(3-methylbut-3-enyl)-2-methylsulfanyl-7h-purin-6-amine Chemical compound CSC1=NC(NCCC(C)=C)=C2NC=NC2=N1 XJVXMWNLQRTRGH-UHFFFAOYSA-N 0.000 description 1
• 210000001989 nasopharynx Anatomy 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 230000036963 noncompetitive effect Effects 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 238000007826 nucleic acid assay Methods 0.000 description 1
• 239000002853 nucleic acid probe Substances 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000002751 oligonucleotide probe Substances 0.000 description 1
• 239000003605 opacifier Substances 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 210000004789 organ system Anatomy 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
• 229960001756 oxaliplatin Drugs 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 210000003695 paranasal sinus Anatomy 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 201000002628 peritoneum cancer Diseases 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000008255 pharmaceutical foam Substances 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 238000003752 polymerase chain reaction Methods 0.000 description 1
• 102000054765 polymorphisms of proteins Human genes 0.000 description 1
• 230000001124 posttranscriptional effect Effects 0.000 description 1
• 230000032361 posttranscriptional gene silencing Effects 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 230000000644 propagated effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 208000023958 prostate neoplasm Diseases 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 210000001938 protoplast Anatomy 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 238000011472 radical prostatectomy Methods 0.000 description 1
• 238000000163 radioactive labelling Methods 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000003753 real-time PCR Methods 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 239000013074 reference sample Substances 0.000 description 1
• 230000002787 reinforcement Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 238000002271 resection Methods 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 229910052702 rhenium Inorganic materials 0.000 description 1
• WUAPFZMCVAUBPE-IGMARMGPSA-N rhenium-186 Chemical compound [186Re] WUAPFZMCVAUBPE-IGMARMGPSA-N 0.000 description 1
• 108091092562 ribozyme Proteins 0.000 description 1
• 238000012502 risk assessment Methods 0.000 description 1
• 201000003804 salivary gland carcinoma Diseases 0.000 description 1
• SIXSYDAISGFNSX-NJFSPNSNSA-N scandium-47 Chemical compound [47Sc] SIXSYDAISGFNSX-NJFSPNSNSA-N 0.000 description 1
• 238000003345 scintillation counting Methods 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• 239000002356 single layer Substances 0.000 description 1
• 239000004055 small Interfering RNA Substances 0.000 description 1
• 230000000391 smoking effect Effects 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000002689 soil Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 210000004988 splenocyte Anatomy 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 208000017572 squamous cell neoplasm Diseases 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 230000003068 static effect Effects 0.000 description 1
• 239000003270 steroid hormone Substances 0.000 description 1
• 229960001052 streptozocin Drugs 0.000 description 1
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 230000004654 survival pathway Effects 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
• 210000000779 thoracic wall Anatomy 0.000 description 1
• 238000003161 three-hybrid assay Methods 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 238000003325 tomography Methods 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000007888 toxin activity Effects 0.000 description 1
• 230000024033 toxin binding Effects 0.000 description 1
• 238000012549 training Methods 0.000 description 1
• 238000010361 transduction Methods 0.000 description 1
• 230000026683 transduction Effects 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 238000011277 treatment modality Methods 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 229930013292 trichothecene Natural products 0.000 description 1
• 150000003327 trichothecene derivatives Chemical class 0.000 description 1
• 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• 238000003160 two-hybrid assay Methods 0.000 description 1
• 241001515965 unidentified phage Species 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 206010046766 uterine cancer Diseases 0.000 description 1
• 208000012991 uterine carcinoma Diseases 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 229960003636 vidarabine Drugs 0.000 description 1
• 210000000605 viral structure Anatomy 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 201000005102 vulva cancer Diseases 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1