CA2697512A1 - Pkib and naaladl2 for target genes of prostate cancer therapy and diagnosis - Google Patents

Info

Publication number

CA2697512A1

CA2697512A1 CA2697512A CA2697512A CA2697512A1 CA 2697512 A1 CA2697512 A1 CA 2697512A1 CA 2697512 A CA2697512 A CA 2697512A CA 2697512 A CA2697512 A CA 2697512A CA 2697512 A1 CA2697512 A1 CA 2697512A1

Authority

CA

Canada

Prior art keywords

pkib

double

naaladl2

prostate cancer

stranded molecule

Prior art date

2007-08-24

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 208000000236 Prostatic Neoplasms Diseases 0.000 title claims abstract description 203
• 206010060862 Prostate cancer Diseases 0.000 title claims abstract description 200
• 101150026024 pkiB gene Proteins 0.000 title claims abstract description 57
• 108090000623 proteins and genes Proteins 0.000 title claims description 220
• 238000003745 diagnosis Methods 0.000 title description 7
• 238000011275 oncology therapy Methods 0.000 title description 3
• 102100023516 cAMP-dependent protein kinase inhibitor beta Human genes 0.000 claims abstract description 353
• 101000978006 Homo sapiens cAMP-dependent protein kinase inhibitor beta Proteins 0.000 claims abstract description 322
• 238000000034 method Methods 0.000 claims abstract description 279
• 101000635408 Homo sapiens Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2 Proteins 0.000 claims abstract description 177
• 102100031009 Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2 Human genes 0.000 claims abstract description 175
• 150000001875 compounds Chemical class 0.000 claims abstract description 129
• 239000013598 vector Substances 0.000 claims abstract description 77
• 239000000203 mixture Substances 0.000 claims abstract description 66
• 206010062904 Hormone-refractory prostate cancer Diseases 0.000 claims abstract description 22
• 230000004663 cell proliferation Effects 0.000 claims abstract description 10
• 101000994505 Drosophila melanogaster cAMP-dependent protein kinase catalytic subunit 1 Proteins 0.000 claims abstract 6
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 169
• 230000014509 gene expression Effects 0.000 claims description 148
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 145
• 102000004169 proteins and genes Human genes 0.000 claims description 132
• 229920001184 polypeptide Polymers 0.000 claims description 131
• 230000027455 binding Effects 0.000 claims description 92
• 206010028980 Neoplasm Diseases 0.000 claims description 90
• 108020004414 DNA Proteins 0.000 claims description 79
• 125000003729 nucleotide group Chemical group 0.000 claims description 79
• 239000002773 nucleotide Substances 0.000 claims description 78
• 230000000692 anti-sense effect Effects 0.000 claims description 75
• 238000012216 screening Methods 0.000 claims description 75
• 201000011510 cancer Diseases 0.000 claims description 73
• 238000012360 testing method Methods 0.000 claims description 66
• 102000040430 polynucleotide Human genes 0.000 claims description 58
• 108091033319 polynucleotide Proteins 0.000 claims description 58
• 239000002157 polynucleotide Substances 0.000 claims description 58
• 230000000694 effects Effects 0.000 claims description 53
• 230000026731 phosphorylation Effects 0.000 claims description 53
• 238000006366 phosphorylation reaction Methods 0.000 claims description 53
• 108091081021 Sense strand Proteins 0.000 claims description 48
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 48
• 230000000295 complement effect Effects 0.000 claims description 48
• 230000004071 biological effect Effects 0.000 claims description 30
• 239000000523 sample Substances 0.000 claims description 27
• 230000002401 inhibitory effect Effects 0.000 claims description 26
• 239000012472 biological sample Substances 0.000 claims description 25
• 238000009396 hybridization Methods 0.000 claims description 23
• 108020004999 messenger RNA Proteins 0.000 claims description 20
• 108700008625 Reporter Genes Proteins 0.000 claims description 15
• 230000001105 regulatory effect Effects 0.000 claims description 15
• 238000001727 in vivo Methods 0.000 claims description 14
• 230000007423 decrease Effects 0.000 claims description 11
• 230000002103 transcriptional effect Effects 0.000 claims description 9
• 210000004369 blood Anatomy 0.000 claims description 7
• 239000008280 blood Substances 0.000 claims description 7
• 230000004942 nuclear accumulation Effects 0.000 claims description 5
• 238000001574 biopsy Methods 0.000 claims description 4
• 210000002700 urine Anatomy 0.000 claims description 4
• 206010036790 Productive cough Diseases 0.000 claims description 3
• 239000006166 lysate Substances 0.000 claims description 3
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 3
• 210000003802 sputum Anatomy 0.000 claims description 3
• 208000024794 sputum Diseases 0.000 claims description 3
• 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 claims 3
• 101150011488 NAALADL2 gene Proteins 0.000 abstract description 54
• 230000002018 overexpression Effects 0.000 abstract description 20
• 230000003993 interaction Effects 0.000 abstract description 15
• 210000000056 organ Anatomy 0.000 abstract description 15
• 230000030570 cellular localization Effects 0.000 abstract 1
• 210000004027 cell Anatomy 0.000 description 292
• 235000018102 proteins Nutrition 0.000 description 125
• 108091008611 Protein Kinase B Proteins 0.000 description 100
• 239000004055 small Interfering RNA Substances 0.000 description 55
• 108020004459 Small interfering RNA Proteins 0.000 description 51
• 239000003795 chemical substances by application Substances 0.000 description 45
• 150000007523 nucleic acids Chemical class 0.000 description 43
• 241000282414 Homo sapiens Species 0.000 description 41
• 239000002502 liposome Substances 0.000 description 39
• 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 34
• 102000039446 nucleic acids Human genes 0.000 description 32
• 108020004707 nucleic acids Proteins 0.000 description 32
• 210000001519 tissue Anatomy 0.000 description 32
• 235000001014 amino acid Nutrition 0.000 description 31
• 150000001413 amino acids Chemical class 0.000 description 29
• 229940024606 amino acid Drugs 0.000 description 28
• 230000010261 cell growth Effects 0.000 description 28
• 239000003814 drug Substances 0.000 description 27
• 239000012634 fragment Substances 0.000 description 27
• 238000004519 manufacturing process Methods 0.000 description 27
• 238000004458 analytical method Methods 0.000 description 26
• 238000003757 reverse transcription PCR Methods 0.000 description 26
• 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 25
• 239000000427 antigen Substances 0.000 description 25
• 108091007433 antigens Proteins 0.000 description 25
• 102000036639 antigens Human genes 0.000 description 25
• 230000004048 modification Effects 0.000 description 25
• 238000012986 modification Methods 0.000 description 25
• 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 24
• 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 24
• 230000012010 growth Effects 0.000 description 24
• 238000003197 gene knockdown Methods 0.000 description 23
• 230000006870 function Effects 0.000 description 21
• BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 20
• 230000037361 pathway Effects 0.000 description 20
• 239000000126 substance Substances 0.000 description 20
• 238000006467 substitution reaction Methods 0.000 description 20
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 19
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 19
• 239000002299 complementary DNA Substances 0.000 description 19
• 229940079593 drug Drugs 0.000 description 19
• 238000011282 treatment Methods 0.000 description 19
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 18
• 230000001965 increasing effect Effects 0.000 description 18
• 201000010099 disease Diseases 0.000 description 17
• 239000000047 product Substances 0.000 description 17
• 108091000080 Phosphotransferase Proteins 0.000 description 16
• 238000000338 in vitro Methods 0.000 description 16
• 102000020233 phosphotransferase Human genes 0.000 description 16
• 239000008194 pharmaceutical composition Substances 0.000 description 15
• 210000002307 prostate Anatomy 0.000 description 15
• -1 BAD Proteins 0.000 description 14
• 108060003951 Immunoglobulin Proteins 0.000 description 14
• 239000013604 expression vector Substances 0.000 description 14
• 102000018358 immunoglobulin Human genes 0.000 description 14
• 102000004190 Enzymes Human genes 0.000 description 13
• 108090000790 Enzymes Proteins 0.000 description 13
• 238000007792 addition Methods 0.000 description 13
• 230000000875 corresponding effect Effects 0.000 description 13
• 238000001514 detection method Methods 0.000 description 13
• 229940088598 enzyme Drugs 0.000 description 13
• 241001465754 Metazoa Species 0.000 description 12
• 239000002202 Polyethylene glycol Substances 0.000 description 12
• 210000000805 cytoplasm Anatomy 0.000 description 12
• 108020001507 fusion proteins Proteins 0.000 description 12
• 102000037865 fusion proteins Human genes 0.000 description 12
• 230000005764 inhibitory process Effects 0.000 description 12
• 229920001223 polyethylene glycol Polymers 0.000 description 12
• 102100032187 Androgen receptor Human genes 0.000 description 11
• 108091028043 Nucleic acid sequence Proteins 0.000 description 11
• 108010080146 androgen receptors Proteins 0.000 description 11
• 239000002246 antineoplastic agent Substances 0.000 description 11
• 230000003247 decreasing effect Effects 0.000 description 11
• 210000004408 hybridoma Anatomy 0.000 description 11
• 229940002612 prodrug Drugs 0.000 description 11
• 239000000651 prodrug Substances 0.000 description 11
• 230000035755 proliferation Effects 0.000 description 11
• 238000010186 staining Methods 0.000 description 11
• 230000008685 targeting Effects 0.000 description 11
• 238000005406 washing Methods 0.000 description 11
• 238000001262 western blot Methods 0.000 description 11
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 10
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 10
• 108091027967 Small hairpin RNA Proteins 0.000 description 10
• 238000013459 approach Methods 0.000 description 10
• 239000013592 cell lysate Substances 0.000 description 10
• 210000002919 epithelial cell Anatomy 0.000 description 10
• 238000011534 incubation Methods 0.000 description 10
• 238000002372 labelling Methods 0.000 description 10
• 239000003446 ligand Substances 0.000 description 10
• 239000013642 negative control Substances 0.000 description 10
• 238000003752 polymerase chain reaction Methods 0.000 description 10
• 230000009467 reduction Effects 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• 230000001225 therapeutic effect Effects 0.000 description 10
• 108090000369 Glutamate Carboxypeptidase II Proteins 0.000 description 9
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 9
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 9
• 239000003098 androgen Substances 0.000 description 9
• 238000003556 assay Methods 0.000 description 9
• 229940127089 cytotoxic agent Drugs 0.000 description 9
• 238000002347 injection Methods 0.000 description 9
• 239000007924 injection Substances 0.000 description 9
• 238000003780 insertion Methods 0.000 description 9
• 230000037431 insertion Effects 0.000 description 9
• 210000004185 liver Anatomy 0.000 description 9
• 230000002265 prevention Effects 0.000 description 9
• 238000012552 review Methods 0.000 description 9
• 238000013519 translation Methods 0.000 description 9
• 238000011144 upstream manufacturing Methods 0.000 description 9
• 102000014914 Carrier Proteins Human genes 0.000 description 8
• 206010035226 Plasma cell myeloma Diseases 0.000 description 8
• 108091008324 binding proteins Proteins 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 238000010276 construction Methods 0.000 description 8
• 238000011161 development Methods 0.000 description 8
• 230000018109 developmental process Effects 0.000 description 8
• 239000001963 growth medium Substances 0.000 description 8
• 210000003734 kidney Anatomy 0.000 description 8
• 210000004072 lung Anatomy 0.000 description 8
• 239000002609 medium Substances 0.000 description 8
• 239000012528 membrane Substances 0.000 description 8
• 201000000050 myeloid neoplasm Diseases 0.000 description 8
• 230000014207 opsonization Effects 0.000 description 8
• 229920001451 polypropylene glycol Polymers 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 238000011321 prophylaxis Methods 0.000 description 8
• 102000005962 receptors Human genes 0.000 description 8
• 108020003175 receptors Proteins 0.000 description 8
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 8
• 230000001629 suppression Effects 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• 238000010396 two-hybrid screening Methods 0.000 description 8
• 241000699666 Mus <mouse, genus> Species 0.000 description 7
• 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 7
• 238000000636 Northern blotting Methods 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 230000003833 cell viability Effects 0.000 description 7
• 238000012217 deletion Methods 0.000 description 7
• 230000037430 deletion Effects 0.000 description 7
• 230000001419 dependent effect Effects 0.000 description 7
• 230000004927 fusion Effects 0.000 description 7
• 230000013595 glycosylation Effects 0.000 description 7
• 238000006206 glycosylation reaction Methods 0.000 description 7
• 210000002216 heart Anatomy 0.000 description 7
• 230000001976 improved effect Effects 0.000 description 7
• 238000001802 infusion Methods 0.000 description 7
• 230000003211 malignant effect Effects 0.000 description 7
• 230000035772 mutation Effects 0.000 description 7
• 230000036961 partial effect Effects 0.000 description 7
• 229920000642 polymer Polymers 0.000 description 7
• 229940043437 protein kinase A inhibitor Drugs 0.000 description 7
• 210000002966 serum Anatomy 0.000 description 7
• 238000013518 transcription Methods 0.000 description 7
• 230000035897 transcription Effects 0.000 description 7
• 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 6
• 108091026890 Coding region Proteins 0.000 description 6
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
• 102100039556 Galectin-4 Human genes 0.000 description 6
• 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 6
• 229910019142 PO4 Inorganic materials 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 239000011324 bead Substances 0.000 description 6
• 230000008901 benefit Effects 0.000 description 6
• 238000012258 culturing Methods 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 239000012216 imaging agent Substances 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 230000003278 mimic effect Effects 0.000 description 6
• 238000002823 phage display Methods 0.000 description 6
• 239000010452 phosphate Substances 0.000 description 6
• 239000013612 plasmid Substances 0.000 description 6
• 239000012656 protein kinase A inhibitor Substances 0.000 description 6
• 230000002441 reversible effect Effects 0.000 description 6
• 238000001890 transfection Methods 0.000 description 6
• 102000053602 DNA Human genes 0.000 description 5
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
• 102000016359 Fibronectins Human genes 0.000 description 5
• 108010067306 Fibronectins Proteins 0.000 description 5
• 108010070675 Glutathione transferase Proteins 0.000 description 5
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
• 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 5
• 101001032478 Homo sapiens cAMP-dependent protein kinase inhibitor alpha Proteins 0.000 description 5
• 238000000134 MTT assay Methods 0.000 description 5
• 231100000002 MTT assay Toxicity 0.000 description 5
• 108010052285 Membrane Proteins Proteins 0.000 description 5
• 102000018697 Membrane Proteins Human genes 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 238000002835 absorbance Methods 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 125000000539 amino acid group Chemical group 0.000 description 5
• 229940049706 benzodiazepine Drugs 0.000 description 5
• 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 5
• 230000008827 biological function Effects 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 102100038086 cAMP-dependent protein kinase inhibitor alpha Human genes 0.000 description 5
• 230000003197 catalytic effect Effects 0.000 description 5
• 238000010293 colony formation assay Methods 0.000 description 5
• 239000002254 cytotoxic agent Substances 0.000 description 5
• 238000005516 engineering process Methods 0.000 description 5
• 230000002255 enzymatic effect Effects 0.000 description 5
• 239000012530 fluid Substances 0.000 description 5
• 239000000499 gel Substances 0.000 description 5
• 239000005556 hormone Substances 0.000 description 5
• 229940088597 hormone Drugs 0.000 description 5
• 238000001114 immunoprecipitation Methods 0.000 description 5
• 150000002632 lipids Chemical class 0.000 description 5
• 238000011068 loading method Methods 0.000 description 5
• 239000002245 particle Substances 0.000 description 5
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
• 229920001282 polysaccharide Polymers 0.000 description 5
• 239000005017 polysaccharide Substances 0.000 description 5
• 150000004804 polysaccharides Chemical class 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• JFINOWIINSTUNY-UHFFFAOYSA-N pyrrolidin-3-ylmethanesulfonamide Chemical compound NS(=O)(=O)CC1CCNC1 JFINOWIINSTUNY-UHFFFAOYSA-N 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 238000011160 research Methods 0.000 description 5
• 230000019491 signal transduction Effects 0.000 description 5
• 239000000243 solution Substances 0.000 description 5
• 238000010561 standard procedure Methods 0.000 description 5
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 5
• 208000024891 symptom Diseases 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 239000000439 tumor marker Substances 0.000 description 5
• 210000005253 yeast cell Anatomy 0.000 description 5
• 108090001008 Avidin Proteins 0.000 description 4
• 241000894006 Bacteria Species 0.000 description 4
• 101000610781 Homo sapiens Proteasome subunit alpha type-2 Proteins 0.000 description 4
• 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 4
• 229930126263 Maytansine Natural products 0.000 description 4
• 206010027476 Metastases Diseases 0.000 description 4
• 241001529936 Murinae Species 0.000 description 4
• 108091034117 Oligonucleotide Proteins 0.000 description 4
• 108700026244 Open Reading Frames Proteins 0.000 description 4
• 241000283973 Oryctolagus cuniculus Species 0.000 description 4
• 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 4
• 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 4
• 102000035195 Peptidases Human genes 0.000 description 4
• 108091005804 Peptidases Proteins 0.000 description 4
• 102000007066 Prostate-Specific Antigen Human genes 0.000 description 4
• 108010072866 Prostate-Specific Antigen Proteins 0.000 description 4
• 102100040364 Proteasome subunit alpha type-2 Human genes 0.000 description 4
• 229920002684 Sepharose Polymers 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 4
• 230000002238 attenuated effect Effects 0.000 description 4
• VTJUKNSKBAOEHE-UHFFFAOYSA-N calixarene Chemical compound COC(=O)COC1=C(CC=2C(=C(CC=3C(=C(C4)C=C(C=3)C(C)(C)C)OCC(=O)OC)C=C(C=2)C(C)(C)C)OCC(=O)OC)C=C(C(C)(C)C)C=C1CC1=C(OCC(=O)OC)C4=CC(C(C)(C)C)=C1 VTJUKNSKBAOEHE-UHFFFAOYSA-N 0.000 description 4
• 150000001720 carbohydrates Chemical class 0.000 description 4
• 238000004113 cell culture Methods 0.000 description 4
• 210000000170 cell membrane Anatomy 0.000 description 4
• 230000001413 cellular effect Effects 0.000 description 4
• 238000007385 chemical modification Methods 0.000 description 4
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
• 238000004590 computer program Methods 0.000 description 4
• 230000002596 correlated effect Effects 0.000 description 4
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 4
• 230000008676 import Effects 0.000 description 4
• 230000002452 interceptive effect Effects 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 108010082117 matrigel Proteins 0.000 description 4
• WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 4
• 230000009401 metastasis Effects 0.000 description 4
• 238000002703 mutagenesis Methods 0.000 description 4
• 231100000350 mutagenesis Toxicity 0.000 description 4
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 229920002401 polyacrylamide Polymers 0.000 description 4
• 238000002360 preparation method Methods 0.000 description 4
• 208000021046 prostate intraepithelial neoplasia Diseases 0.000 description 4
• 150000003839 salts Chemical class 0.000 description 4
• 230000004960 subcellular localization Effects 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 210000004881 tumor cell Anatomy 0.000 description 4
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
• 229920002307 Dextran Polymers 0.000 description 3
• 241000588724 Escherichia coli Species 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• 108091006027 G proteins Proteins 0.000 description 3
• 102000030782 GTP binding Human genes 0.000 description 3
• 108091000058 GTP-Binding Proteins 0.000 description 3
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 3
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
• 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 3
• 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 3
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
• 108060001084 Luciferase Proteins 0.000 description 3
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
• 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 3
• 238000007807 Matrigel invasion assay Methods 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 229930040373 Paraformaldehyde Natural products 0.000 description 3
• 108010067902 Peptide Library Proteins 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 241000283984 Rodentia Species 0.000 description 3
• 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 3
• 102100022056 Serum response factor Human genes 0.000 description 3
• 108091081024 Start codon Proteins 0.000 description 3
• 238000000692 Student's t-test Methods 0.000 description 3
• 239000004473 Threonine Substances 0.000 description 3
• 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 3
• 230000001594 aberrant effect Effects 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 230000004075 alteration Effects 0.000 description 3
• 229940041181 antineoplastic drug Drugs 0.000 description 3
• 230000001588 bifunctional effect Effects 0.000 description 3
• 229960002685 biotin Drugs 0.000 description 3
• 235000020958 biotin Nutrition 0.000 description 3
• 239000011616 biotin Substances 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 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 3
• 230000015556 catabolic process Effects 0.000 description 3
• 230000024245 cell differentiation Effects 0.000 description 3
• 230000005754 cellular signaling Effects 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 238000010367 cloning Methods 0.000 description 3
• 238000005094 computer simulation Methods 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
• 231100000433 cytotoxic Toxicity 0.000 description 3
• 231100000599 cytotoxic agent Toxicity 0.000 description 3
• 230000001472 cytotoxic effect Effects 0.000 description 3
• 238000006731 degradation reaction Methods 0.000 description 3
• 239000005547 deoxyribonucleotide Substances 0.000 description 3
• 238000013461 design Methods 0.000 description 3
• 230000004069 differentiation Effects 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 239000012091 fetal bovine serum Substances 0.000 description 3
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
• 210000004602 germ cell Anatomy 0.000 description 3
• 102000044994 human PKIB Human genes 0.000 description 3
• 229910052739 hydrogen Inorganic materials 0.000 description 3
• 230000016784 immunoglobulin production Effects 0.000 description 3
• 238000002991 immunohistochemical analysis Methods 0.000 description 3
• 206010022000 influenza Diseases 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 101150066555 lacZ gene Proteins 0.000 description 3
• 210000004698 lymphocyte Anatomy 0.000 description 3
• 238000010369 molecular cloning Methods 0.000 description 3
• 230000000955 neuroendocrine Effects 0.000 description 3
• 230000007935 neutral effect Effects 0.000 description 3
• 229920002866 paraformaldehyde Polymers 0.000 description 3
• 230000001575 pathological effect Effects 0.000 description 3
• 239000000816 peptidomimetic Substances 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 230000001766 physiological effect Effects 0.000 description 3
• 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 3
• 230000002285 radioactive effect Effects 0.000 description 3
• 235000000346 sugar Nutrition 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 239000003053 toxin Substances 0.000 description 3
• 231100000765 toxin Toxicity 0.000 description 3
• 108700012359 toxins Proteins 0.000 description 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
• VPFUWHKTPYPNGT-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)propan-1-one Chemical compound OC1=C2C=CC(C)(C)OC2=CC=C1C(=O)CCC1=CC=C(O)C(O)=C1 VPFUWHKTPYPNGT-UHFFFAOYSA-N 0.000 description 2
• CERZMXAJYMMUDR-QBTAGHCHSA-N 5-amino-3,5-dideoxy-D-glycero-D-galacto-non-2-ulopyranosonic acid Chemical compound N[C@@H]1[C@@H](O)CC(O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO CERZMXAJYMMUDR-QBTAGHCHSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• 229920000936 Agarose Polymers 0.000 description 2
• 101710186708 Agglutinin Proteins 0.000 description 2
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
• 206010003445 Ascites Diseases 0.000 description 2
• 102100026189 Beta-galactosidase Human genes 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 102000005600 Cathepsins Human genes 0.000 description 2
• 108010084457 Cathepsins Proteins 0.000 description 2
• 108020004635 Complementary DNA Proteins 0.000 description 2
• 101710205889 Cytochrome b562 Proteins 0.000 description 2
• SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
• 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 description 2
• 102100031780 Endonuclease Human genes 0.000 description 2
• 241000724791 Filamentous phage Species 0.000 description 2
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 2
• 239000004471 Glycine Substances 0.000 description 2
• 108090000288 Glycoproteins Proteins 0.000 description 2
• 102000003886 Glycoproteins Human genes 0.000 description 2
• HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 2
• 101150009006 HIS3 gene Proteins 0.000 description 2
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
• 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 2
• 101001117143 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial Proteins 0.000 description 2
• 101710146024 Horcolin Proteins 0.000 description 2
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 2
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 101710189395 Lectin Proteins 0.000 description 2
• 102000019298 Lipocalin Human genes 0.000 description 2
• 108050006654 Lipocalin Proteins 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 101710179758 Mannose-specific lectin Proteins 0.000 description 2
• 101710150763 Mannose-specific lectin 1 Proteins 0.000 description 2
• 101710150745 Mannose-specific lectin 2 Proteins 0.000 description 2
• 241000699660 Mus musculus Species 0.000 description 2
• 102000043276 Oncogene Human genes 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
• 108010039918 Polylysine Proteins 0.000 description 2
• 208000004965 Prostatic Intraepithelial Neoplasia Diseases 0.000 description 2
• 206010071019 Prostatic dysplasia Diseases 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
• 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 2
• 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 2
• 238000010240 RT-PCR analysis Methods 0.000 description 2
• 108020004511 Recombinant DNA Proteins 0.000 description 2
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
• 108091028664 Ribonucleotide Proteins 0.000 description 2
• 108010039491 Ricin Proteins 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• 102000039471 Small Nuclear RNA Human genes 0.000 description 2
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 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
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
• 108091036066 Three prime untranslated region Proteins 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
• 101710120037 Toxin CcdB Proteins 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 102100024150 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial Human genes 0.000 description 2
• 238000010317 ablation therapy Methods 0.000 description 2
• 238000001042 affinity chromatography Methods 0.000 description 2
• 239000000910 agglutinin Substances 0.000 description 2
• 239000000556 agonist Substances 0.000 description 2
• 235000004279 alanine Nutrition 0.000 description 2
• 238000012867 alanine scanning Methods 0.000 description 2
• 230000003321 amplification Effects 0.000 description 2
• 230000001093 anti-cancer Effects 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 238000011888 autopsy Methods 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• 108010005774 beta-Galactosidase Proteins 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 229940098773 bovine serum albumin Drugs 0.000 description 2
• 238000004422 calculation algorithm Methods 0.000 description 2
• 229930195731 calicheamicin Natural products 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 101150055766 cat gene Proteins 0.000 description 2
• 238000000423 cell based assay Methods 0.000 description 2
• 238000010609 cell counting kit-8 assay Methods 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 238000006243 chemical reaction Methods 0.000 description 2
• 235000012000 cholesterol Nutrition 0.000 description 2
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
• 230000021615 conjugation Effects 0.000 description 2
• 229920001577 copolymer Polymers 0.000 description 2
• 239000003431 cross linking reagent Substances 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 238000003235 crystal violet staining Methods 0.000 description 2
• 235000018417 cysteine Nutrition 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 230000008021 deposition Effects 0.000 description 2
• 230000000368 destabilizing effect Effects 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000001378 electrochemiluminescence detection Methods 0.000 description 2
• 238000004520 electroporation Methods 0.000 description 2
• 210000000981 epithelium Anatomy 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 229960002949 fluorouracil Drugs 0.000 description 2
• 235000019152 folic acid Nutrition 0.000 description 2
• 150000002224 folic acids Chemical class 0.000 description 2
• 238000001502 gel electrophoresis Methods 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 102000053563 human MYC Human genes 0.000 description 2
• 229920002674 hyaluronan Polymers 0.000 description 2
• 229960003160 hyaluronic acid Drugs 0.000 description 2
• 229920001477 hydrophilic polymer Polymers 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
• 230000003053 immunization Effects 0.000 description 2
• 238000002649 immunization Methods 0.000 description 2
• 238000003018 immunoassay Methods 0.000 description 2
• 229940127121 immunoconjugate Drugs 0.000 description 2
• 238000003365 immunocytochemistry Methods 0.000 description 2
• 230000002163 immunogen Effects 0.000 description 2
• 238000003364 immunohistochemistry Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000001361 intraarterial administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000005304 joining Methods 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 230000004807 localization Effects 0.000 description 2
• 229920001427 mPEG Polymers 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000035800 maturation Effects 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 229930182817 methionine Natural products 0.000 description 2
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
• 238000001531 micro-dissection Methods 0.000 description 2
• 238000010208 microarray analysis Methods 0.000 description 2
• 102000035118 modified proteins Human genes 0.000 description 2
• 108091005573 modified proteins Proteins 0.000 description 2
• 238000000329 molecular dynamics simulation Methods 0.000 description 2
• 238000000302 molecular modelling Methods 0.000 description 2
• 210000000865 mononuclear phagocyte system Anatomy 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 230000030648 nucleus localization Effects 0.000 description 2
• 238000011580 nude mouse model Methods 0.000 description 2
• 229920001542 oligosaccharide Chemical class 0.000 description 2
• 150000002482 oligosaccharides Chemical class 0.000 description 2
• 238000010397 one-hybrid screening Methods 0.000 description 2
• 238000010647 peptide synthesis reaction Methods 0.000 description 2
• 108040007629 peroxidase activity proteins Proteins 0.000 description 2
• 102000013415 peroxidase activity proteins Human genes 0.000 description 2
• 229940124531 pharmaceutical excipient Drugs 0.000 description 2
• 150000008104 phosphatidylethanolamines Chemical group 0.000 description 2
• 150000004713 phosphodiesters Chemical class 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 210000002826 placenta Anatomy 0.000 description 2
• 229920000962 poly(amidoamine) Polymers 0.000 description 2
• 229920000656 polylysine Polymers 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 238000004393 prognosis Methods 0.000 description 2
• 230000000644 propagated effect Effects 0.000 description 2
• 150000003212 purines Chemical class 0.000 description 2
• 238000003127 radioimmunoassay Methods 0.000 description 2
• 238000001959 radiotherapy Methods 0.000 description 2
• 238000002708 random mutagenesis Methods 0.000 description 2
• 230000006798 recombination Effects 0.000 description 2
• 238000005215 recombination Methods 0.000 description 2
• 102000037983 regulatory factors Human genes 0.000 description 2
• 108091008025 regulatory factors Proteins 0.000 description 2
• 239000002336 ribonucleotide Substances 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 150000003384 small molecules Chemical class 0.000 description 2
• 108091029842 small nuclear ribonucleic acid Proteins 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 229910001415 sodium ion Inorganic materials 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 230000000392 somatic effect Effects 0.000 description 2
• 230000003595 spectral effect Effects 0.000 description 2
• 210000000952 spleen Anatomy 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 238000010254 subcutaneous injection Methods 0.000 description 2
• 239000007929 subcutaneous injection Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• 229910052721 tungsten Inorganic materials 0.000 description 2
• 238000003160 two-hybrid assay Methods 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 230000035899 viability Effects 0.000 description 2
• 239000013603 viral vector Substances 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• 238000012800 visualization Methods 0.000 description 2
• 229910052727 yttrium Inorganic materials 0.000 description 2
• KYBXNPIASYUWLN-WUCPZUCCSA-N (2s)-5-hydroxypyrrolidine-2-carboxylic acid Chemical compound OC1CC[C@@H](C(O)=O)N1 KYBXNPIASYUWLN-WUCPZUCCSA-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
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-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
• FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
• FBUTXZSKZCQABC-UHFFFAOYSA-N 2-amino-1-methyl-7h-purine-6-thione Chemical compound S=C1N(C)C(N)=NC2=C1NC=N2 FBUTXZSKZCQABC-UHFFFAOYSA-N 0.000 description 1
• 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 108020005345 3' Untranslated Regions Proteins 0.000 description 1
• HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 description 1
• FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
• 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
• 229940117976 5-hydroxylysine Drugs 0.000 description 1
• TWGNOYAGHYUFFR-UHFFFAOYSA-N 5-methylpyrimidine Chemical group CC1=CN=CN=C1 TWGNOYAGHYUFFR-UHFFFAOYSA-N 0.000 description 1
• LMEHJKJEPRYEEB-UHFFFAOYSA-N 5-prop-1-ynylpyrimidine Chemical compound CC#CC1=CN=CN=C1 LMEHJKJEPRYEEB-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• 108010066676 Abrin Proteins 0.000 description 1
• 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• 102000000132 Alpha tubulin Human genes 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 102100031890 Aminopeptidase NAALADL1 Human genes 0.000 description 1
• 108020005544 Antisense RNA Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 208000002109 Argyria Diseases 0.000 description 1
• 102000009133 Arylsulfatases Human genes 0.000 description 1
• 101000669426 Aspergillus restrictus Ribonuclease mitogillin Proteins 0.000 description 1
• 101710192393 Attachment protein G3P Proteins 0.000 description 1
• 241000193738 Bacillus anthracis Species 0.000 description 1
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 101001059929 Caenorhabditis elegans Forkhead box protein O Proteins 0.000 description 1
• 101100346189 Caenorhabditis elegans mpc-1 gene Proteins 0.000 description 1
• 101100421200 Caenorhabditis elegans sep-1 gene Proteins 0.000 description 1
• 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• 101710158575 Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase Proteins 0.000 description 1
• 101710169873 Capsid protein G8P Proteins 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 102000005367 Carboxypeptidases Human genes 0.000 description 1
• 108010006303 Carboxypeptidases Proteins 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• 108091035707 Consensus sequence Proteins 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 239000004971 Cross linker Substances 0.000 description 1
• 108700032819 Croton tiglium crotin II Proteins 0.000 description 1
• 235000019750 Crude protein Nutrition 0.000 description 1
• 241001559589 Cullen Species 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• 102000000311 Cytosine Deaminase Human genes 0.000 description 1
• 108010080611 Cytosine Deaminase Proteins 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 150000008574 D-amino acids Chemical group 0.000 description 1
• AEMOLEFTQBMNLQ-VANFPWTGSA-N D-mannopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-VANFPWTGSA-N 0.000 description 1
• 230000004544 DNA amplification Effects 0.000 description 1
• 108010053770 Deoxyribonucleases Proteins 0.000 description 1
• 102000016911 Deoxyribonucleases Human genes 0.000 description 1
• 241000702421 Dependoparvovirus Species 0.000 description 1
• 108010016626 Dipeptides Proteins 0.000 description 1
• 102000016607 Diphtheria Toxin Human genes 0.000 description 1
• 108010053187 Diphtheria Toxin Proteins 0.000 description 1
• 241000006271 Discosoma sp. 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
• 101710202200 Endolysin A Proteins 0.000 description 1
• 108010042407 Endonucleases Proteins 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 108700039887 Essential Genes Proteins 0.000 description 1
• 101710082714 Exotoxin A Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 208000000666 Fowlpox Diseases 0.000 description 1
• 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 description 1
• 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101100079343 Homo sapiens NAALADL1 gene Proteins 0.000 description 1
• 101001105486 Homo sapiens Proteasome subunit alpha type-7 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
• 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
• 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 1
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 239000012097 Lipofectamine 2000 Substances 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 101001133631 Lysinibacillus sphaericus Penicillin acylase Proteins 0.000 description 1
• 101710125418 Major capsid protein Proteins 0.000 description 1
• 101710156564 Major tail protein Gp23 Proteins 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 244000302512 Momordica charantia Species 0.000 description 1
• 235000009811 Momordica charantia Nutrition 0.000 description 1
• 101100293261 Mus musculus Naa15 gene Proteins 0.000 description 1
• 101001059625 Mytilus californianus Fibronectin type III domain-containing protein Proteins 0.000 description 1
• 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 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
• 230000004988 N-glycosylation Effects 0.000 description 1
• 101150082943 NAT1 gene Proteins 0.000 description 1
• 108091061960 Naked DNA Proteins 0.000 description 1
• 102000005348 Neuraminidase Human genes 0.000 description 1
• 108010006232 Neuraminidase Proteins 0.000 description 1
• 108090000189 Neuropeptides Proteins 0.000 description 1
• 108091092724 Noncoding DNA Proteins 0.000 description 1
• 239000004677 Nylon Substances 0.000 description 1
• 230000004989 O-glycosylation Effects 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
• 101100081884 Oryza sativa subsp. japonica OSA15 gene Proteins 0.000 description 1
• 102000042712 PKI family Human genes 0.000 description 1
• 108091081628 PKI family Proteins 0.000 description 1
• 101150082245 PSAG gene Proteins 0.000 description 1
• 239000002033 PVDF binder Substances 0.000 description 1
• 229920002230 Pectic acid Polymers 0.000 description 1
• 108010073038 Penicillin Amidase Proteins 0.000 description 1
• 101710123388 Penicillin G acylase Proteins 0.000 description 1
• 108091093037 Peptide nucleic acid Proteins 0.000 description 1
• 241000009328 Perro Species 0.000 description 1
• 101100413173 Phytolacca americana PAP2 gene Proteins 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 229920002873 Polyethylenimine Polymers 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
• 102100021201 Proteasome subunit alpha type-7 Human genes 0.000 description 1
• 101800004937 Protein C Proteins 0.000 description 1
• 102000017975 Protein C Human genes 0.000 description 1
• 244000007021 Prunus avium Species 0.000 description 1
• 235000010401 Prunus avium Nutrition 0.000 description 1
• 239000012083 RIPA buffer Substances 0.000 description 1
• 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
• 238000011579 SCID mouse model Methods 0.000 description 1
• 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
• WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
• 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 description 1
• 101800001700 Saposin-D Proteins 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 241000607720 Serratia Species 0.000 description 1
• 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
• 108020004682 Single-Stranded DNA Proteins 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 229930182558 Sterol Natural products 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 108090000787 Subtilisin Proteins 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
• 244000247617 Teramnus labialis var. labialis Species 0.000 description 1
• 108090001109 Thermolysin Proteins 0.000 description 1
• 108010034949 Thyroglobulin Proteins 0.000 description 1
• 102000009843 Thyroglobulin Human genes 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 229940122618 Trypsin inhibitor Drugs 0.000 description 1
• 101710162629 Trypsin inhibitor Proteins 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 108090000704 Tubulin Proteins 0.000 description 1
• 108091023045 Untranslated Region Proteins 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 101150117115 V gene Proteins 0.000 description 1
• 241000700618 Vaccinia virus Species 0.000 description 1
• 206010046865 Vaccinia virus infection Diseases 0.000 description 1
• 244000156473 Vallaris heynei Species 0.000 description 1
• 240000001866 Vernicia fordii Species 0.000 description 1
• 241000711975 Vesicular stomatitis virus Species 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 235000021068 Western diet Nutrition 0.000 description 1
• 238000002441 X-ray diffraction Methods 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 230000035508 accumulation Effects 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 108020002494 acetyltransferase Proteins 0.000 description 1
• 102000005421 acetyltransferase Human genes 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 229940009456 adriamycin Drugs 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000011543 agarose gel Substances 0.000 description 1
• 238000000246 agarose gel electrophoresis Methods 0.000 description 1
• 230000004931 aggregating effect Effects 0.000 description 1
• 230000032683 aging Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
• IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
• 108010001818 alpha-sarcin Proteins 0.000 description 1
• 229940037003 alum Drugs 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229960003896 aminopterin Drugs 0.000 description 1
• 210000004381 amniotic fluid Anatomy 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 238000000137 annealing Methods 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 230000001857 anti-mycotic effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 210000000628 antibody-producing cell Anatomy 0.000 description 1
• 102000025171 antigen binding proteins Human genes 0.000 description 1
• 108091000831 antigen binding proteins Proteins 0.000 description 1
• 239000002543 antimycotic Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 238000002306 biochemical method Methods 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 239000012620 biological material Substances 0.000 description 1
• 238000005460 biophysical method Methods 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 238000007470 bone biopsy Methods 0.000 description 1
• 229960005069 calcium Drugs 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011692 calcium ascorbate Substances 0.000 description 1
• 235000010376 calcium ascorbate Nutrition 0.000 description 1
• 229940047036 calcium ascorbate Drugs 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 229960002713 calcium chloride Drugs 0.000 description 1
• 235000011148 calcium chloride Nutrition 0.000 description 1
• 239000004227 calcium gluconate Substances 0.000 description 1
• 235000013927 calcium gluconate Nutrition 0.000 description 1
• 229960004494 calcium gluconate Drugs 0.000 description 1
• MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
• 239000001527 calcium lactate Substances 0.000 description 1
• 229960002401 calcium lactate Drugs 0.000 description 1
• 235000011086 calcium lactate Nutrition 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
• BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 description 1
• NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
• BHRQIJRLOVHRKH-UHFFFAOYSA-L calcium;2-[bis[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate;hydron Chemical compound [Ca+2].OC(=O)CN(CC(O)=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O BHRQIJRLOVHRKH-UHFFFAOYSA-L 0.000 description 1
• 230000009702 cancer cell proliferation Effects 0.000 description 1
• 230000005773 cancer-related death Effects 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 150000004653 carbonic acids Chemical class 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 239000000679 carrageenan Substances 0.000 description 1
• 229920001525 carrageenan Polymers 0.000 description 1
• 235000010418 carrageenan Nutrition 0.000 description 1
• 229940113118 carrageenan Drugs 0.000 description 1
• 238000012219 cassette mutagenesis Methods 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000022534 cell killing Effects 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 238000010382 chemical cross-linking Methods 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 238000000546 chi-square test Methods 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 230000005757 colony formation Effects 0.000 description 1
• 230000001332 colony forming effect Effects 0.000 description 1
• 239000003184 complementary RNA Substances 0.000 description 1
• 238000012790 confirmation Methods 0.000 description 1
• 230000001268 conjugating effect Effects 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 239000012228 culture supernatant Substances 0.000 description 1
• 210000004748 cultured cell Anatomy 0.000 description 1
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 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 description 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• 101150047356 dec-1 gene Proteins 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
• 238000004925 denaturation Methods 0.000 description 1
• 230000036425 denaturation Effects 0.000 description 1
• 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
• 239000003599 detergent Substances 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 229930191339 dianthin Natural products 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 125000005442 diisocyanate group Chemical group 0.000 description 1
• 206010013023 diphtheria Diseases 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 1
• 229960003668 docetaxel Drugs 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 108010028531 enomycin Proteins 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
• 101150032670 est gene Proteins 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 238000004880 explosion Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 210000004700 fetal blood Anatomy 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 108010021843 fluorescent protein 583 Proteins 0.000 description 1
• 150000002222 fluorine compounds Chemical class 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000005194 fractionation Methods 0.000 description 1
• 238000013467 fragmentation Methods 0.000 description 1
• 238000006062 fragmentation reaction Methods 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• QPJBWNIQKHGLAU-IQZHVAEDSA-N ganglioside GM1 Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 QPJBWNIQKHGLAU-IQZHVAEDSA-N 0.000 description 1
• 150000002270 gangliosides Chemical class 0.000 description 1
• 238000003500 gene array Methods 0.000 description 1
• 238000003208 gene overexpression Methods 0.000 description 1
• 230000030279 gene silencing Effects 0.000 description 1
• 230000009368 gene silencing by RNA Effects 0.000 description 1
• 102000034356 gene-regulatory proteins Human genes 0.000 description 1
• 108091006104 gene-regulatory proteins Proteins 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 229940097043 glucuronic acid Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
• 238000013537 high throughput screening Methods 0.000 description 1
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
• 238000002744 homologous recombination Methods 0.000 description 1
• 230000006801 homologous recombination Effects 0.000 description 1
• 150000001469 hydantoins Chemical class 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
• 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 150000002463 imidates Chemical class 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000008105 immune reaction Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 210000004201 immune sera Anatomy 0.000 description 1
• 229940042743 immune sera Drugs 0.000 description 1
• 230000009851 immunogenic response Effects 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 238000012744 immunostaining Methods 0.000 description 1
• 230000002637 immunotoxin Effects 0.000 description 1
• 229940051026 immunotoxin Drugs 0.000 description 1
• 239000002596 immunotoxin Substances 0.000 description 1
• 231100000608 immunotoxin Toxicity 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 238000007689 inspection Methods 0.000 description 1
• 238000009830 intercalation Methods 0.000 description 1
• 230000002687 intercalation Effects 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 230000002601 intratumoral effect Effects 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• MKXZASYAUGDDCJ-CGTJXYLNSA-N levomethorphan Chemical compound C([C@H]12)CCC[C@@]11CCN(C)[C@@H]2CC2=CC=C(OC)C=C21 MKXZASYAUGDDCJ-CGTJXYLNSA-N 0.000 description 1
• 230000001926 lymphatic effect Effects 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000005389 magnetism Effects 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 108010010621 modeccin Proteins 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 210000003097 mucus Anatomy 0.000 description 1
• 108091005763 multidomain proteins Proteins 0.000 description 1
• 239000005445 natural material Substances 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 238000013188 needle biopsy Methods 0.000 description 1
• 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
• 230000017095 negative regulation of cell growth Effects 0.000 description 1
• CERZMXAJYMMUDR-UHFFFAOYSA-N neuraminic acid Natural products NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO CERZMXAJYMMUDR-UHFFFAOYSA-N 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 230000030147 nuclear export Effects 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 238000007826 nucleic acid assay Methods 0.000 description 1
• 238000013392 nude mouse xenograft model Methods 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 229920001778 nylon Polymers 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 239000002751 oligonucleotide probe Substances 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 125000000885 organic scaffold group Chemical group 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 239000003002 pH adjusting agent Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
• 125000001151 peptidyl group Chemical group 0.000 description 1
• 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
• 235000020030 perry Nutrition 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 108010076042 phenomycin Proteins 0.000 description 1
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
• NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 150000003905 phosphatidylinositols Chemical class 0.000 description 1
• 150000003906 phosphoinositides Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 201000008814 placenta cancer Diseases 0.000 description 1
• 239000000419 plant extract Substances 0.000 description 1
• 239000013600 plasmid vector Substances 0.000 description 1
• 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
• 108010054442 polyalanine Proteins 0.000 description 1
• 239000010318 polygalacturonic acid Substances 0.000 description 1
• 229920002704 polyhistidine Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
• 238000010837 poor prognosis Methods 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 230000002980 postoperative effect Effects 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• 238000009117 preventive therapy Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000009862 primary prevention Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 210000005267 prostate cell Anatomy 0.000 description 1
• 208000023958 prostate neoplasm Diseases 0.000 description 1
• 235000019833 protease Nutrition 0.000 description 1
• 235000019419 proteases Nutrition 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 229960000856 protein c Drugs 0.000 description 1
• 230000012743 protein tagging Effects 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 150000003235 pyrrolidines Chemical class 0.000 description 1
• 238000011472 radical prostatectomy Methods 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 238000003259 recombinant expression Methods 0.000 description 1
• 238000010188 recombinant method Methods 0.000 description 1
• 108010054624 red fluorescent protein Proteins 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 239000013074 reference sample Substances 0.000 description 1
• 238000002271 resection Methods 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 230000001177 retroviral effect Effects 0.000 description 1
• PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
• 108010008790 ribosomal phosphoprotein P1 Proteins 0.000 description 1
• 229920002477 rna polymer Polymers 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 238000013391 scatchard analysis Methods 0.000 description 1
• 210000000582 semen Anatomy 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000010703 silicon Substances 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 230000003007 single stranded DNA break Effects 0.000 description 1
• 238000002741 site-directed mutagenesis Methods 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 239000006104 solid solution Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 238000001179 sorption measurement Methods 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000007447 staining method Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 238000000528 statistical test Methods 0.000 description 1
• 235000003702 sterols Nutrition 0.000 description 1
• 150000003432 sterols Chemical class 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 229940014800 succinic anhydride Drugs 0.000 description 1
• 150000005846 sugar alcohols Polymers 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 108060007951 sulfatase Proteins 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000002344 surface layer Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 210000001179 synovial fluid Anatomy 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 229920003002 synthetic resin Polymers 0.000 description 1
• 239000000057 synthetic resin Substances 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• 150000003505 terpenes Chemical class 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 229960002175 thyroglobulin Drugs 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 230000014621 translational initiation Effects 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 230000032258 transport Effects 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
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229940073585 tromethamine hydrochloride Drugs 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241001515965 unidentified phage Species 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 208000007089 vaccinia Diseases 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 229910052720 vanadium Inorganic materials 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• WQAJKOXBERTWBK-UHFFFAOYSA-N verdine Natural products CC1CNC2C(C1)OC3(CCC4C5CCC6(O)CC(O)CC(O)C6(C)C5C(=O)C4=C3C)C2C WQAJKOXBERTWBK-UHFFFAOYSA-N 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1