CA2813101C - Eph receptor expression in tumor stem cells - Google Patents
Eph receptor expression in tumor stem cells Download PDFInfo
- Publication number
- CA2813101C CA2813101C CA2813101A CA2813101A CA2813101C CA 2813101 C CA2813101 C CA 2813101C CA 2813101 A CA2813101 A CA 2813101A CA 2813101 A CA2813101 A CA 2813101A CA 2813101 C CA2813101 C CA 2813101C
- Authority
- CA
- Canada
- Prior art keywords
- cells
- epha2
- gbm
- use according
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 125
- 210000000130 stem cell Anatomy 0.000 title claims abstract description 59
- 230000014509 gene expression Effects 0.000 title claims description 67
- 108091008815 Eph receptors Proteins 0.000 title claims description 48
- 102000050554 Eph Family Receptors Human genes 0.000 title claims description 47
- 108010055196 EphA2 Receptor Proteins 0.000 claims abstract description 106
- 201000011510 cancer Diseases 0.000 claims abstract description 48
- 102000051096 EphA2 Receptor Human genes 0.000 claims abstract description 46
- 230000012010 growth Effects 0.000 claims abstract description 30
- 208000003174 Brain Neoplasms Diseases 0.000 claims abstract description 28
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 25
- 239000002243 precursor Substances 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 238000011321 prophylaxis Methods 0.000 claims abstract description 5
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 3
- 210000004027 cell Anatomy 0.000 claims description 194
- 208000005017 glioblastoma Diseases 0.000 claims description 122
- 230000000694 effects Effects 0.000 claims description 57
- 230000004663 cell proliferation Effects 0.000 claims description 13
- 201000010915 Glioblastoma multiforme Diseases 0.000 claims description 11
- 230000012292 cell migration Effects 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 5
- 238000002271 resection Methods 0.000 claims description 5
- 230000001413 cellular effect Effects 0.000 claims description 3
- 108060003951 Immunoglobulin Proteins 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 102000018358 immunoglobulin Human genes 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 1
- 230000035755 proliferation Effects 0.000 abstract description 13
- 230000002401 inhibitory effect Effects 0.000 abstract description 9
- 210000003169 central nervous system Anatomy 0.000 abstract description 5
- 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 62
- 241000282414 Homo sapiens Species 0.000 description 54
- 239000003112 inhibitor Substances 0.000 description 46
- 239000003446 ligand Substances 0.000 description 35
- 108020003175 receptors Proteins 0.000 description 35
- 102000005962 receptors Human genes 0.000 description 35
- 238000011282 treatment Methods 0.000 description 35
- 241000699666 Mus <mouse, genus> Species 0.000 description 34
- 238000004458 analytical method Methods 0.000 description 30
- 241000283973 Oryctolagus cuniculus Species 0.000 description 27
- 241000283707 Capra Species 0.000 description 26
- 210000001519 tissue Anatomy 0.000 description 26
- 241000699670 Mus sp. Species 0.000 description 25
- 230000002441 reversible effect Effects 0.000 description 21
- 238000000338 in vitro Methods 0.000 description 18
- 238000001727 in vivo Methods 0.000 description 18
- 238000002347 injection Methods 0.000 description 17
- 239000007924 injection Substances 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 16
- 239000002609 medium Substances 0.000 description 15
- 230000026731 phosphorylation Effects 0.000 description 15
- 238000006366 phosphorylation reaction Methods 0.000 description 15
- 230000004614 tumor growth Effects 0.000 description 14
- 230000004913 activation Effects 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 210000004881 tumor cell Anatomy 0.000 description 12
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 11
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 11
- 230000008901 benefit Effects 0.000 description 11
- 230000005754 cellular signaling Effects 0.000 description 11
- 238000001262 western blot Methods 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 230000003247 decreasing effect Effects 0.000 description 10
- 238000000684 flow cytometry Methods 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- 210000001178 neural stem cell Anatomy 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 102000007469 Actins Human genes 0.000 description 9
- 108010085238 Actins Proteins 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- 230000003828 downregulation Effects 0.000 description 9
- 230000003211 malignant effect Effects 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 210000001577 neostriatum Anatomy 0.000 description 9
- 239000013598 vector Substances 0.000 description 9
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 8
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- 230000005012 migration Effects 0.000 description 8
- 238000013508 migration Methods 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 238000010186 staining Methods 0.000 description 8
- 238000007920 subcutaneous administration Methods 0.000 description 8
- 230000000381 tumorigenic effect Effects 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 7
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 7
- 108060002566 ephrin Proteins 0.000 description 7
- 102000012803 ephrin Human genes 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 238000001000 micrograph Methods 0.000 description 7
- 230000000284 resting effect Effects 0.000 description 7
- 238000002054 transplantation Methods 0.000 description 7
- 206010018338 Glioma Diseases 0.000 description 6
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 239000013592 cell lysate Substances 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 238000010494 dissociation reaction Methods 0.000 description 6
- 230000005593 dissociations Effects 0.000 description 6
- 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 6
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 6
- 238000002513 implantation Methods 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- -1 EphA10 Proteins 0.000 description 5
- 241000283074 Equus asinus Species 0.000 description 5
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 5
- 102100037813 Focal adhesion kinase 1 Human genes 0.000 description 5
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 5
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 241000021375 Xenogenes Species 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 238000005415 bioluminescence Methods 0.000 description 5
- 230000029918 bioluminescence Effects 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 5
- 239000005090 green fluorescent protein Substances 0.000 description 5
- 238000003364 immunohistochemistry Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000001537 neural effect Effects 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 238000011002 quantification Methods 0.000 description 5
- 230000007480 spreading Effects 0.000 description 5
- 210000005102 tumor initiating cell Anatomy 0.000 description 5
- 231100000588 tumorigenic Toxicity 0.000 description 5
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 4
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 4
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 4
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 4
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 4
- 208000032612 Glial tumor Diseases 0.000 description 4
- 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 4
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 4
- 108010009711 Phalloidine Proteins 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 239000007640 basal medium Substances 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000003636 conditioned culture medium Substances 0.000 description 4
- 230000003436 cytoskeletal effect Effects 0.000 description 4
- 210000004292 cytoskeleton Anatomy 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 238000007747 plating Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000003757 reverse transcription PCR Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229960001722 verapamil Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000012103 Alexa Fluor 488 Substances 0.000 description 3
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 3
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 3
- 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 3
- 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 3
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 3
- 102100032352 Leukemia inhibitory factor Human genes 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 229940124647 MEK inhibitor Drugs 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000002457 bidirectional effect Effects 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000009643 clonogenic assay Methods 0.000 description 3
- 231100000096 clonogenic assay Toxicity 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 238000009650 gentamicin protection assay Methods 0.000 description 3
- 238000003119 immunoblot Methods 0.000 description 3
- 238000003125 immunofluorescent labeling Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000007917 intracranial administration Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000001617 migratory effect Effects 0.000 description 3
- 230000004660 morphological change Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 239000003656 tris buffered saline Substances 0.000 description 3
- 230000005740 tumor formation Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 108020004463 18S ribosomal RNA Proteins 0.000 description 2
- 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 2
- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 description 2
- ZAINTDRBUHCDPZ-UHFFFAOYSA-M Alexa Fluor 546 Chemical compound [H+].[Na+].CC1CC(C)(C)NC(C(=C2OC3=C(C4=NC(C)(C)CC(C)C4=CC3=3)S([O-])(=O)=O)S([O-])(=O)=O)=C1C=C2C=3C(C(=C(Cl)C=1Cl)C(O)=O)=C(Cl)C=1SCC(=O)NCCCCCC(=O)ON1C(=O)CCC1=O ZAINTDRBUHCDPZ-UHFFFAOYSA-M 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 102000000905 Cadherin Human genes 0.000 description 2
- 108050007957 Cadherin Proteins 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 108050006400 Cyclin Proteins 0.000 description 2
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 description 2
- 108010055191 EphA3 Receptor Proteins 0.000 description 2
- 108010055179 EphA4 Receptor Proteins 0.000 description 2
- 108010055182 EphA5 Receptor Proteins 0.000 description 2
- 108010055153 EphA7 Receptor Proteins 0.000 description 2
- 108010055155 EphA8 Receptor Proteins 0.000 description 2
- 108010055334 EphB2 Receptor Proteins 0.000 description 2
- 102100030322 Ephrin type-A receptor 1 Human genes 0.000 description 2
- 102100030324 Ephrin type-A receptor 3 Human genes 0.000 description 2
- 102100021616 Ephrin type-A receptor 4 Human genes 0.000 description 2
- 102100021605 Ephrin type-A receptor 5 Human genes 0.000 description 2
- 102100021606 Ephrin type-A receptor 7 Human genes 0.000 description 2
- 102100021601 Ephrin type-A receptor 8 Human genes 0.000 description 2
- 102100030779 Ephrin type-B receptor 1 Human genes 0.000 description 2
- 102100031982 Ephrin type-B receptor 3 Human genes 0.000 description 2
- 102100031983 Ephrin type-B receptor 4 Human genes 0.000 description 2
- 102100033919 Ephrin-A2 Human genes 0.000 description 2
- 102100033940 Ephrin-A3 Human genes 0.000 description 2
- 102100033942 Ephrin-A4 Human genes 0.000 description 2
- 102100033941 Ephrin-A5 Human genes 0.000 description 2
- 108010043939 Ephrin-A5 Proteins 0.000 description 2
- 102100033946 Ephrin-B1 Human genes 0.000 description 2
- 108010044099 Ephrin-B1 Proteins 0.000 description 2
- 102100023721 Ephrin-B2 Human genes 0.000 description 2
- 102100023733 Ephrin-B3 Human genes 0.000 description 2
- 108010044085 Ephrin-B3 Proteins 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108090000331 Firefly luciferases Proteins 0.000 description 2
- 101000938354 Homo sapiens Ephrin type-A receptor 1 Proteins 0.000 description 2
- 101000938346 Homo sapiens Ephrin type-A receptor 2 Proteins 0.000 description 2
- 101001064150 Homo sapiens Ephrin type-B receptor 1 Proteins 0.000 description 2
- 101001064458 Homo sapiens Ephrin type-B receptor 3 Proteins 0.000 description 2
- 101000925269 Homo sapiens Ephrin-A2 Proteins 0.000 description 2
- 101000925241 Homo sapiens Ephrin-A3 Proteins 0.000 description 2
- 101000925259 Homo sapiens Ephrin-A4 Proteins 0.000 description 2
- 101001049392 Homo sapiens Ephrin-B2 Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-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
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 108010090306 Member 2 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 2
- 102000013013 Member 2 Subfamily G ATP Binding Cassette Transporter Human genes 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 102000009339 Proliferating Cell Nuclear Antigen Human genes 0.000 description 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000004958 brain cell Anatomy 0.000 description 2
- 210000005103 brain tumor initiating cell Anatomy 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 239000013000 chemical inhibitor Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000003021 clonogenic effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000030609 dephosphorylation Effects 0.000 description 2
- 238000006209 dephosphorylation reaction Methods 0.000 description 2
- 230000000779 depleting effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- MURGITYSBWUQTI-UHFFFAOYSA-N fluorescin Chemical compound OC(=O)C1=CC=CC=C1C1C2=CC=C(O)C=C2OC2=CC(O)=CC=C21 MURGITYSBWUQTI-UHFFFAOYSA-N 0.000 description 2
- 239000012909 foetal bovine serum Substances 0.000 description 2
- 101150022753 galc gene Proteins 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000003365 immunocytochemistry Methods 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 238000011503 in vivo imaging Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000006662 intracellular pathway Effects 0.000 description 2
- 238000010212 intracellular staining Methods 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 210000004248 oligodendroglia Anatomy 0.000 description 2
- 230000005959 oncogenic signaling Effects 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000013643 reference control Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000008054 signal transmission Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 2
- 229960000977 trabectedin Drugs 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 1
- SNBCLPGEMZEWLU-QXFUBDJGSA-N 2-chloro-n-[[(2r,3s,5r)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl]acetamide Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CNC(=O)CCl)[C@@H](O)C1 SNBCLPGEMZEWLU-QXFUBDJGSA-N 0.000 description 1
- LCSKNASZPVZHEG-UHFFFAOYSA-N 3,6-dimethyl-1,4-dioxane-2,5-dione;1,4-dioxane-2,5-dione Chemical group O=C1COC(=O)CO1.CC1OC(=O)C(C)OC1=O LCSKNASZPVZHEG-UHFFFAOYSA-N 0.000 description 1
- UPXRTVAIJMUAQR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CC1NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 UPXRTVAIJMUAQR-UHFFFAOYSA-N 0.000 description 1
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 description 1
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 238000010599 BrdU assay Methods 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 102100031277 Calcineurin B homologous protein 1 Human genes 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 239000012594 Earle’s Balanced Salt Solution Substances 0.000 description 1
- 101710116743 Ephrin type-A receptor 2 Proteins 0.000 description 1
- 102100031984 Ephrin type-B receptor 6 Human genes 0.000 description 1
- 102100040954 Ephrin-A1 Human genes 0.000 description 1
- 108010043945 Ephrin-A1 Proteins 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
- 108010039731 Fatty Acid Synthases Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000004878 Gelsolin Human genes 0.000 description 1
- 108090001064 Gelsolin Proteins 0.000 description 1
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 1
- 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 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 1
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101001064451 Homo sapiens Ephrin type-B receptor 6 Proteins 0.000 description 1
- 101000965523 Homo sapiens Ephrin-A1 Proteins 0.000 description 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- FGBAVQUHSKYMTC-UHFFFAOYSA-M LDS 751 dye Chemical compound [O-]Cl(=O)(=O)=O.C1=CC2=CC(N(C)C)=CC=C2[N+](CC)=C1C=CC=CC1=CC=C(N(C)C)C=C1 FGBAVQUHSKYMTC-UHFFFAOYSA-M 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 1
- 102000046795 Mitogen-Activated Protein Kinase 3 Human genes 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100451971 Mus musculus Ephx2 gene Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 102000038030 PI3Ks Human genes 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 108010030544 Peptidyl-Lys metalloendopeptidase Proteins 0.000 description 1
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 229920000153 Povidone-iodine Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 239000005700 Putrescine Substances 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 101710149279 Small delta antigen Proteins 0.000 description 1
- 238000012288 TUNEL assay Methods 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 101150109862 WNT-5A gene Proteins 0.000 description 1
- 108700020483 Wnt-5a Proteins 0.000 description 1
- 102000043366 Wnt-5a Human genes 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 230000018486 cell cycle phase Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011278 co-treatment Methods 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000013211 curve analysis Methods 0.000 description 1
- 230000002380 cytological effect Effects 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 230000029578 entry into host Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 208000002854 epidermolysis bullosa simplex superficialis Diseases 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001046 green dye Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000009033 hematopoietic malignancy Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 102000046148 human BMP4 Human genes 0.000 description 1
- QYRFJLLXPINATB-UHFFFAOYSA-N hydron;2,4,5,6-tetrafluorobenzene-1,3-diamine;dichloride Chemical compound Cl.Cl.NC1=C(F)C(N)=C(F)C(F)=C1F QYRFJLLXPINATB-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003312 immunocapture Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000005732 intercellular adhesion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960004184 ketamine hydrochloride Drugs 0.000 description 1
- 238000010983 kinetics study Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 208000030173 low grade glioma Diseases 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000004031 neuronal differentiation Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 238000013326 plasmid cotransfection Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 229960001621 povidone-iodine Drugs 0.000 description 1
- 230000001566 pro-viral effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 239000003531 protein hydrolysate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000033300 receptor internalization Effects 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 210000001646 side-population cell Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000003518 stress fiber Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000000564 temperature-controlled scanning calorimetry Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Marine Sciences & Fisheries (AREA)
- Dermatology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10185930A EP2446895A1 (en) | 2010-10-01 | 2010-10-01 | EPH receptor expression in tumor stem cells |
| EP10185930.4 | 2010-10-01 | ||
| PCT/EP2011/067114 WO2012042021A1 (en) | 2010-10-01 | 2011-09-30 | Eph receptor expression in tumor stem cells |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2813101A1 CA2813101A1 (en) | 2012-04-05 |
| CA2813101C true CA2813101C (en) | 2018-10-30 |
Family
ID=43856109
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2813101A Active CA2813101C (en) | 2010-10-01 | 2011-09-30 | Eph receptor expression in tumor stem cells |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US9078857B2 (cg-RX-API-DMAC7.html) |
| EP (2) | EP2446895A1 (cg-RX-API-DMAC7.html) |
| JP (4) | JP2013540117A (cg-RX-API-DMAC7.html) |
| KR (2) | KR101719966B1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2011310109B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2813101C (cg-RX-API-DMAC7.html) |
| DK (1) | DK2621513T3 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2616444T3 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ609594A (cg-RX-API-DMAC7.html) |
| PL (1) | PL2621513T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2012042021A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140031175A (ko) | 2010-12-08 | 2014-03-12 | 스템 센트알엑스 인코포레이티드 | 신규 조절제 및 용법 |
| SA112330278B1 (ar) | 2011-02-18 | 2015-10-09 | ستيم سينتركس، انك. | مواد ضابطة جديدة وطرق للاستخدام |
| EP2733206A1 (en) * | 2012-11-19 | 2014-05-21 | Naroa LLC | Method for the isolation for mammalian stem cells using EphA2 and uses thereof |
| BR112016010051A2 (pt) | 2013-11-04 | 2017-12-05 | Pfizer | ?conjugados de anticorpo-fármaco anti-efna4? |
| EP3137114B8 (en) | 2014-04-30 | 2021-08-04 | Pfizer Inc. | Anti-ptk7 antibody-drug conjugates |
| KR102674191B1 (ko) | 2014-12-10 | 2024-06-11 | 하이퍼스템 에스에이 | 뇌암 줄기 세포의 성장, 이동 및 침습성 감소 그리고 뇌종양을 가진 환자의 생존 개선 방법 및 조성물 |
| US10783439B2 (en) * | 2015-05-08 | 2020-09-22 | FlowJo, LLC | Plugin interface and framework for integrating a remote server with sample data analysis software |
| EP3373939A4 (en) | 2015-11-10 | 2019-06-26 | B.G. Negev Technologies and Applications Ltd., at Ben-Gurion University | MEDIUM AND METHOD FOR REDUCING TUMORIGENITY OF CANCER STEM CELLS |
| JP7680047B2 (ja) * | 2020-03-31 | 2025-05-20 | 慶應義塾 | ゲノム編集多能性幹細胞を用いた治療薬 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050281783A1 (en) * | 2003-10-15 | 2005-12-22 | Kinch Michael S | Listeria-based EphA2 vaccines |
| EP1778726A4 (en) * | 2004-08-16 | 2009-03-18 | Medimmune Inc | INTEGRIN ANTAGONISTS WITH IMPROVED ANTIBODY-DEPENDENT CELL-ASSAYED CYTOTOXICITY ACTIVITY |
| US20070248628A1 (en) * | 2005-12-06 | 2007-10-25 | Keller Lorraine H | Immunogens in cancer stem cells |
| US8343461B2 (en) * | 2006-03-08 | 2013-01-01 | Wake Forest University Health Sciences | Molecular signature of cancer |
| RU2525133C2 (ru) * | 2007-08-30 | 2014-08-10 | Дайити Санкио Компани, Лимитед | Антитело к epha2 |
-
2010
- 2010-10-01 EP EP10185930A patent/EP2446895A1/en not_active Withdrawn
-
2011
- 2011-04-18 US US13/089,217 patent/US9078857B2/en active Active
- 2011-09-30 KR KR1020167002577A patent/KR101719966B1/ko active Active
- 2011-09-30 NZ NZ609594A patent/NZ609594A/en unknown
- 2011-09-30 KR KR1020137011310A patent/KR20130095286A/ko not_active Ceased
- 2011-09-30 ES ES11778540.2T patent/ES2616444T3/es active Active
- 2011-09-30 JP JP2013530753A patent/JP2013540117A/ja active Pending
- 2011-09-30 CA CA2813101A patent/CA2813101C/en active Active
- 2011-09-30 DK DK11778540.2T patent/DK2621513T3/en active
- 2011-09-30 WO PCT/EP2011/067114 patent/WO2012042021A1/en not_active Ceased
- 2011-09-30 PL PL11778540T patent/PL2621513T3/pl unknown
- 2011-09-30 EP EP11778540.2A patent/EP2621513B1/en active Active
- 2011-09-30 AU AU2011310109A patent/AU2011310109B2/en active Active
-
2015
- 2015-10-09 JP JP2015200808A patent/JP6523910B2/ja active Active
-
2017
- 2017-10-02 JP JP2017192907A patent/JP6618968B2/ja active Active
-
2019
- 2019-11-13 JP JP2019205190A patent/JP2020037579A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP2621513A1 (en) | 2013-08-07 |
| KR20160027106A (ko) | 2016-03-09 |
| JP2020037579A (ja) | 2020-03-12 |
| JP6618968B2 (ja) | 2019-12-11 |
| JP2018048151A (ja) | 2018-03-29 |
| NZ609594A (en) | 2015-01-30 |
| KR101719966B1 (ko) | 2017-03-24 |
| CA2813101A1 (en) | 2012-04-05 |
| DK2621513T3 (en) | 2017-03-06 |
| ES2616444T3 (es) | 2017-06-13 |
| AU2011310109A1 (en) | 2013-05-02 |
| US9078857B2 (en) | 2015-07-14 |
| WO2012042021A1 (en) | 2012-04-05 |
| JP2013540117A (ja) | 2013-10-31 |
| JP6523910B2 (ja) | 2019-06-05 |
| PL2621513T3 (pl) | 2017-06-30 |
| EP2621513B1 (en) | 2016-12-28 |
| EP2446895A1 (en) | 2012-05-02 |
| AU2011310109B2 (en) | 2014-11-20 |
| KR20130095286A (ko) | 2013-08-27 |
| JP2016094391A (ja) | 2016-05-26 |
| US20120083454A1 (en) | 2012-04-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2813101C (en) | Eph receptor expression in tumor stem cells | |
| Zhang et al. | Interleukin-11 treatment protected against cerebral ischemia/reperfusion injury | |
| AU2015359043C1 (en) | Methods and compositions for reducing growth, migration and invasiveness of brain cancer stem cells and improving survival of patients with brian tumors | |
| Atherton et al. | Sympathetic modulation of tumor necrosis factor alpha-induced nociception in the presence of oral squamous cell carcinoma | |
| Maisel et al. | Stapled EGFR peptide reduces inflammatory breast cancer and inhibits additional HER-driven models of cancer | |
| Fang et al. | Enhanced cell growth and tumorigenicity of rat glioma cells by stable expression of human CD133 through multiple molecular actions | |
| Abdelazeem et al. | Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC | |
| US20230190718A1 (en) | Methods for the treatment of pancreatitis and prevention of pancreatic cancer | |
| Ding et al. | The effects of pleiotrophin in proliferative vitreoretinopathy | |
| Jung et al. | The role of endothelin receptor A during myelination of developing oligodendrocytes | |
| US12123000B2 (en) | Use of PI3KC2B inhibitors for the preservation of vascular endothelial cell barrier integrity | |
| WO2015153967A1 (en) | MITOTIC KINESIN Eg5 INHIBITING ANTICANCER AGENTS | |
| KR20200017495A (ko) | Nk-92 세포 및 il-15 효능제의 조합 요법 | |
| KR20240052739A (ko) | 급성 골수성 백혈병 치료를 위한 wnt5a | |
| Gomez et al. | Aberrant hypothalamic neuronal activity blunts glucocorticoid diurnal rhythms in murine breast cancer | |
| Joshi | Hypoxic Regulation of Angiotensin-Converting Enzyme 2 and Mas Receptor in Hematopoietic Stem/Progenitor Cells: A Translational Study | |
| CN113144170A (zh) | 肽及其在调节巨核细胞分化、治疗血小板相关疾病中的应用 | |
| Ma | Mechanisms of Brain Edema Formation in Mouse Models of Intracerebral Hemorrhage | |
| Koodie | Effects of chronic morphine treatment on tumor angiogenesis and growth | |
| SDA | THE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1 MONOCLONAL ANTIBODY D16F7 INHIBITS GLIOMA GROWTH AND ANGIOGENESIS IN VIVO | |
| Wright | Role and regulation of G-CSF and its receptor in muscle | |
| Nickerson | Transforming Growth Factor Beta Signaling in Growth of Estrogen-Insensitive Metastatic Bone Lesions | |
| Walker | The role of stromal cell-derived factor-1 in cell mobilization, cell homing, and neovascularization following stroke | |
| Peeters et al. | PACAP mediated megakaryopoiesis and thrombopoiesis for the treatment of thrombocytopenia | |
| Miller | The negative regulatory effects of LRIG1 on ErbB and Met receptor tyrosine kinases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20160707 |