CA2443378A1 - Methods of screening and using inhibitors of angiogenesis - Google Patents
Methods of screening and using inhibitors of angiogenesis Download PDFInfo
- Publication number
- CA2443378A1 CA2443378A1 CA002443378A CA2443378A CA2443378A1 CA 2443378 A1 CA2443378 A1 CA 2443378A1 CA 002443378 A CA002443378 A CA 002443378A CA 2443378 A CA2443378 A CA 2443378A CA 2443378 A1 CA2443378 A1 CA 2443378A1
- Authority
- CA
- Canada
- Prior art keywords
- alpha
- integrin
- subunit
- mmp
- angiogenesis
- 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.)
- Abandoned
Links
- 230000033115 angiogenesis Effects 0.000 title claims abstract description 47
- 238000000034 method Methods 0.000 title claims abstract description 29
- 238000012216 screening Methods 0.000 title claims abstract description 6
- 239000003112 inhibitor Substances 0.000 title description 6
- 102000006495 integrins Human genes 0.000 claims abstract description 116
- 108010044426 integrins Proteins 0.000 claims abstract description 116
- 230000004913 activation Effects 0.000 claims abstract description 23
- 230000001575 pathological effect Effects 0.000 claims abstract description 8
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 230000014509 gene expression Effects 0.000 claims description 69
- 102000011716 Matrix Metalloproteinase 14 Human genes 0.000 claims description 33
- 108010076557 Matrix Metalloproteinase 14 Proteins 0.000 claims description 33
- 230000006427 angiogenic response Effects 0.000 claims description 31
- 230000005012 migration Effects 0.000 claims description 8
- 238000013508 migration Methods 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 238000003776 cleavage reaction Methods 0.000 claims description 5
- 230000007017 scission Effects 0.000 claims description 5
- 230000008859 change Effects 0.000 claims description 3
- 238000001962 electrophoresis Methods 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims description 2
- 108700008625 Reporter Genes Proteins 0.000 claims 2
- 238000001514 detection method Methods 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 6
- 206010038923 Retinopathy Diseases 0.000 abstract description 4
- 208000002780 macular degeneration Diseases 0.000 abstract description 4
- 201000011510 cancer Diseases 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 210000004087 cornea Anatomy 0.000 description 53
- 238000010186 staining Methods 0.000 description 53
- 210000001519 tissue Anatomy 0.000 description 48
- 102000004266 Collagen Type IV Human genes 0.000 description 38
- 108010042086 Collagen Type IV Proteins 0.000 description 38
- 210000005166 vasculature Anatomy 0.000 description 38
- 230000000694 effects Effects 0.000 description 33
- 102000007000 Tenascin Human genes 0.000 description 25
- 108010008125 Tenascin Proteins 0.000 description 25
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 22
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 22
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 21
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 21
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 21
- 210000002889 endothelial cell Anatomy 0.000 description 21
- 239000013615 primer Substances 0.000 description 20
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 19
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 19
- 208000027418 Wounds and injury Diseases 0.000 description 19
- 108091034117 Oligonucleotide Proteins 0.000 description 18
- 108010067306 Fibronectins Proteins 0.000 description 17
- 102000016359 Fibronectins Human genes 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 108010085895 Laminin Proteins 0.000 description 15
- 102000007547 Laminin Human genes 0.000 description 15
- 230000004044 response Effects 0.000 description 15
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 14
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 14
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 14
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 14
- 208000014674 injury Diseases 0.000 description 14
- 230000001404 mediated effect Effects 0.000 description 14
- 238000007805 zymography Methods 0.000 description 14
- 230000002491 angiogenic effect Effects 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 102000001690 Factor VIII Human genes 0.000 description 12
- 108010054218 Factor VIII Proteins 0.000 description 12
- 230000006378 damage Effects 0.000 description 12
- 229960000301 factor viii Drugs 0.000 description 12
- 206010029113 Neovascularisation Diseases 0.000 description 11
- 210000002744 extracellular matrix Anatomy 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000011161 development Methods 0.000 description 10
- 230000018109 developmental process Effects 0.000 description 10
- 238000011065 in-situ storage Methods 0.000 description 10
- 230000007998 vessel formation Effects 0.000 description 10
- 102000005741 Metalloproteases Human genes 0.000 description 9
- 108010006035 Metalloproteases Proteins 0.000 description 9
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000035800 maturation Effects 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 238000003757 reverse transcription PCR Methods 0.000 description 9
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
- 238000007804 gelatin zymography Methods 0.000 description 8
- 238000012744 immunostaining Methods 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 6
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 210000002469 basement membrane Anatomy 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000004807 localization Effects 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 206010052428 Wound Diseases 0.000 description 5
- 239000002870 angiogenesis inducing agent Substances 0.000 description 5
- 230000021164 cell adhesion Effects 0.000 description 5
- 239000000833 heterodimer Substances 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- 102000004856 Lectins Human genes 0.000 description 4
- 108090001090 Lectins Proteins 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 206010003246 arthritis Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 201000000159 corneal neovascularization Diseases 0.000 description 4
- 210000003683 corneal stroma Anatomy 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000010166 immunofluorescence Methods 0.000 description 4
- 238000002991 immunohistochemical analysis Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 239000002523 lectin Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000013382 Gelatinases Human genes 0.000 description 3
- 108010026132 Gelatinases Proteins 0.000 description 3
- 102100034343 Integrase Human genes 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- 238000010240 RT-PCR analysis Methods 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 102000019997 adhesion receptor Human genes 0.000 description 3
- 108010013985 adhesion receptor Proteins 0.000 description 3
- 230000004709 cell invasion Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 3
- 230000001023 pro-angiogenic effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000007634 remodeling Methods 0.000 description 3
- 230000002123 temporal effect Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000028006 Corneal injury Diseases 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- KCLANYCVBBTKTO-UHFFFAOYSA-N Proparacaine Chemical compound CCCOC1=CC=C(C(=O)OCCN(CC)CC)C=C1N KCLANYCVBBTKTO-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 235000013290 Sagittaria latifolia Nutrition 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 206010064996 Ulcerative keratitis Diseases 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000001772 anti-angiogenic effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 235000015246 common arrowhead Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004624 confocal microscopy Methods 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000010393 epithelial cell migration Effects 0.000 description 2
- 210000003560 epithelium corneal Anatomy 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000003668 pericyte Anatomy 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 229960003981 proparacaine Drugs 0.000 description 2
- 229910001961 silver nitrate Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 230000004862 vasculogenesis Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- HKJKONMZMPUGHJ-UHFFFAOYSA-N 4-amino-5-hydroxy-3-[(4-nitrophenyl)diazenyl]-6-phenyldiazenylnaphthalene-2,7-disulfonic acid Chemical compound OS(=O)(=O)C1=CC2=CC(S(O)(=O)=O)=C(N=NC=3C=CC=CC=3)C(O)=C2C(N)=C1N=NC1=CC=C([N+]([O-])=O)C=C1 HKJKONMZMPUGHJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 101710197641 Actin-5 Proteins 0.000 description 1
- 102000012936 Angiostatins Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 241000486679 Antitype Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010055665 Corneal neovascularisation Diseases 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- 206010015911 Eye burns Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 208000007135 Retinal Neovascularization Diseases 0.000 description 1
- 238000012233 TRIzol extraction Methods 0.000 description 1
- 102100038126 Tenascin Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 1
- 229960005054 acepromazine Drugs 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000027735 angiogenesis involved in wound healing Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 238000000339 bright-field microscopy Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000000408 embryogenic effect Effects 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 102000036444 extracellular matrix enzymes Human genes 0.000 description 1
- 108091007167 extracellular matrix enzymes Proteins 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
- 238000010230 functional analysis Methods 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
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- -1 however Proteins 0.000 description 1
- 229960000900 human factor viii Drugs 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000010185 immunofluorescence analysis Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 229940048282 ketamine 100 mg/ml Drugs 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000005868 ontogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002441 reversible 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
- 210000002966 serum Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- JGVWCANSWKRBCS-UHFFFAOYSA-N tetramethylrhodamine thiocyanate Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=C(SC#N)C=C1C(O)=O JGVWCANSWKRBCS-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000007556 vascular defect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940110150 xylazine 20 mg/ml Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
- C12Q1/37—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving peptidase or proteinase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70546—Integrin superfamily, e.g. VLAs, leuCAM, GPIIb/GPIIIa, LPAM
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
- G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
- G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
- G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
- G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
- G01N2333/96486—Metalloendopeptidases (3.4.24)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pathology (AREA)
- Toxicology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biophysics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28151201P | 2001-04-04 | 2001-04-04 | |
| US60/281,512 | 2001-04-04 | ||
| PCT/US2002/010501 WO2002081627A2 (en) | 2001-04-04 | 2002-04-03 | Methods of screening and using inhibitors of angiogenesis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2443378A1 true CA2443378A1 (en) | 2002-10-17 |
Family
ID=23077607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002443378A Abandoned CA2443378A1 (en) | 2001-04-04 | 2002-04-03 | Methods of screening and using inhibitors of angiogenesis |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US20030171271A1 (enExample) |
| EP (1) | EP1393075A4 (enExample) |
| JP (1) | JP2005506524A (enExample) |
| CA (1) | CA2443378A1 (enExample) |
| WO (1) | WO2002081627A2 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8574827B2 (en) | 2002-10-29 | 2013-11-05 | Rigel Pharmaceuticals, Inc. | Modulators of angiogenesis and tumorigenesis |
| WO2005080984A1 (en) * | 2004-02-17 | 2005-09-01 | Rigel Pharmaceuticals, Incorporated | Modulators of angiogenesis and tumorigenesis |
| HRP20130782T1 (en) * | 2004-04-02 | 2013-09-30 | The Regents Of The University Of California, Office Of Technology Transfer | Methods and compositions for treating and preventing disease associated with alpha v beta 5 integrin |
| NO323175B1 (no) | 2004-12-23 | 2007-01-15 | Jan O Aasly | Framgangsmate for a pavise en mutasjon som forarsaker arvelig parkinsonisme |
| EP2456460A4 (en) | 2009-07-24 | 2013-02-20 | Univ California | METHOD AND COMPOSITIONS FOR TREATING AND PREVENTING DISEASES ASSOCIATED WITH AVB5 INTEGRIN |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6022948A (en) * | 1996-09-17 | 2000-02-08 | Washington University | Method of cell surface activation and inhibition |
-
2002
- 2002-04-03 JP JP2002579991A patent/JP2005506524A/ja not_active Withdrawn
- 2002-04-03 US US10/115,718 patent/US20030171271A1/en not_active Abandoned
- 2002-04-03 WO PCT/US2002/010501 patent/WO2002081627A2/en not_active Ceased
- 2002-04-03 EP EP02763922A patent/EP1393075A4/en not_active Withdrawn
- 2002-04-03 CA CA002443378A patent/CA2443378A1/en not_active Abandoned
-
2003
- 2003-10-29 US US10/697,487 patent/US20040126825A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1393075A4 (en) | 2006-06-14 |
| US20030171271A1 (en) | 2003-09-11 |
| US20040126825A1 (en) | 2004-07-01 |
| EP1393075A2 (en) | 2004-03-03 |
| JP2005506524A (ja) | 2005-03-03 |
| WO2002081627A2 (en) | 2002-10-17 |
| WO2002081627A3 (en) | 2003-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Expression of integrins and MMPs during alkaline-burn-induced corneal angiogenesis | |
| US10940179B2 (en) | Therapeutic compositions for the treatment of dry eye disease | |
| Azar | Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis) | |
| Andreasen et al. | The urokinase‐type plasminogen activator system in cancer metastasis: a review | |
| Vince et al. | Heterogeneous regional expression patterns of matrix metalloproteinases in human malignant gliomas | |
| Loukovaara et al. | Indications of lymphatic endothelial differentiation and endothelial progenitor cell activation in the pathology of proliferative diabetic retinopathy | |
| JP2006507297A (ja) | ケロイドおよび他の皮膚または内部創傷または病変における異常瘢痕形成の処置および予防 | |
| Keller et al. | Differential effects of ADAMTS-1,-4, and-5 in the trabecular meshwork | |
| Bjørn et al. | Messenger RNA for membrane-type 2 matrix metalloproteinase, MT2-MMP, is expressed in human placenta of first trimester | |
| CA2443378A1 (en) | Methods of screening and using inhibitors of angiogenesis | |
| CA2494870A1 (en) | Methods for inhibiting angiogenesis | |
| Sivak et al. | Pharmacologic uncoupling of angiogenesis and inflammation during initiation of pathological corneal neovascularization | |
| AU2002307096A1 (en) | Methods of screening and using inhibitors of angiogenesis | |
| Alapure et al. | Matrix metalloproteinase-9 activity in human lens epithelial cells of cortical, posterior subcapsular, and nuclear cataracts | |
| Nagavarapu et al. | Membrane type 1 matrix metalloproteinase regulates cellular invasiveness and survival in cutaneous epidermal cells | |
| JP2007530538A (ja) | 過剰血管新生と関連する疾患の処置のためのｅｍｍｐｒｉｎアンタゴニストの使用 | |
| Warejcka et al. | Differential conversion of plasminogen to angiostatin by human corneal cell populations | |
| US20050214302A1 (en) | Use of emmprin antagonists for the treatment of diseases associated with excessive angiogenesis | |
| Masos et al. | Plasminogen activator inhibitor-1 mRNA is localized in the ciliary epithelium of the rodent eye | |
| EP3096780A1 (en) | Abl1 inhibitor for treating and preventing ocular neovascularisation | |
| US20030108530A1 (en) | Antisense inhibiting melanoma invasion and functional analogs thereof | |
| Yeow | Functional analysis of sorsby's fundus dystrophy mutant TIMP-3 | |
| JP2004522702A (ja) | 血管形成の調節 | |
| Cordeiro | The role of transforming growth factor-β (TGF-β) in the conjunctival scarring process following glaucoma surgery | |
| RONALD | HOST EXTRACELLULAR MATRICES |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |