CA2344370A1 - Chemokine receptor antagonist and cyclosporin in combined therapy - Google Patents
Chemokine receptor antagonist and cyclosporin in combined therapy Download PDFInfo
- Publication number
- CA2344370A1 CA2344370A1 CA002344370A CA2344370A CA2344370A1 CA 2344370 A1 CA2344370 A1 CA 2344370A1 CA 002344370 A CA002344370 A CA 002344370A CA 2344370 A CA2344370 A CA 2344370A CA 2344370 A1 CA2344370 A1 CA 2344370A1
- Authority
- CA
- Canada
- Prior art keywords
- rantes
- cyclosporin
- receptor antagonist
- chemokine receptor
- cells
- 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
- 108010036949 Cyclosporine Proteins 0.000 title claims abstract description 41
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 title claims abstract description 40
- 229930105110 Cyclosporin A Natural products 0.000 title claims abstract description 40
- 229960001265 ciclosporin Drugs 0.000 title claims abstract description 40
- 229930182912 cyclosporin Natural products 0.000 title claims abstract description 23
- 229940122444 Chemokine receptor antagonist Drugs 0.000 title claims abstract description 22
- 239000002559 chemokine receptor antagonist Substances 0.000 title claims abstract description 22
- 238000002648 combination therapy Methods 0.000 title description 3
- 108010023347 Met- RANTES Proteins 0.000 claims abstract description 44
- 210000000056 organ Anatomy 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 239000004480 active ingredient Substances 0.000 claims abstract description 10
- 238000002054 transplantation Methods 0.000 claims description 25
- 108010012236 Chemokines Proteins 0.000 claims description 15
- 102000019034 Chemokines Human genes 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000002207 metabolite Substances 0.000 claims description 4
- 108010055166 Chemokine CCL5 Proteins 0.000 claims 2
- 102000001327 Chemokine CCL5 Human genes 0.000 claims 2
- 206010052779 Transplant rejections Diseases 0.000 abstract description 11
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 210000003734 kidney Anatomy 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 35
- 210000001616 monocyte Anatomy 0.000 description 28
- 241001465754 Metazoa Species 0.000 description 24
- 210000005063 microvascular endothelium Anatomy 0.000 description 20
- 230000014509 gene expression Effects 0.000 description 19
- 238000000034 method Methods 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 15
- 241000700159 Rattus Species 0.000 description 13
- 230000006378 damage Effects 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 230000000694 effects Effects 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 210000005087 mononuclear cell Anatomy 0.000 description 10
- 108010002352 Interleukin-1 Proteins 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 230000008595 infiltration Effects 0.000 description 9
- 238000001764 infiltration Methods 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000003511 endothelial effect Effects 0.000 description 8
- 210000003038 endothelium Anatomy 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 7
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 210000000265 leukocyte Anatomy 0.000 description 7
- 238000011694 lewis rat Methods 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- 230000002792 vascular Effects 0.000 description 7
- 102000015689 E-Selectin Human genes 0.000 description 6
- 108010024212 E-Selectin Proteins 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 208000024248 Vascular System injury Diseases 0.000 description 6
- 208000012339 Vascular injury Diseases 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 108700012920 TNF Proteins 0.000 description 5
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 5
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 210000002889 endothelial cell Anatomy 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000007480 spreading Effects 0.000 description 5
- 210000005239 tubule Anatomy 0.000 description 5
- 206010062016 Immunosuppression Diseases 0.000 description 4
- 102000006382 Ribonucleases Human genes 0.000 description 4
- 108010083644 Ribonucleases Proteins 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 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 4
- 230000001506 immunosuppresive effect Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000007115 recruitment Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 101710187886 60S ribosomal protein L30 Proteins 0.000 description 3
- 102100040768 60S ribosomal protein L32 Human genes 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010051392 Diapedesis Diseases 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 238000000585 Mann–Whitney U test Methods 0.000 description 3
- 206010029155 Nephropathy toxic Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 230000003872 anastomosis Effects 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 230000002500 effect on skin Effects 0.000 description 3
- 210000003979 eosinophil Anatomy 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 102000006495 integrins Human genes 0.000 description 3
- 108010044426 integrins Proteins 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 230000007694 nephrotoxicity Effects 0.000 description 3
- 231100000417 nephrotoxicity Toxicity 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 238000005096 rolling process Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 210000000626 ureter Anatomy 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 108050000299 Chemokine receptor Proteins 0.000 description 2
- 102000009410 Chemokine receptor Human genes 0.000 description 2
- 108010036941 Cyclosporins Proteins 0.000 description 2
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 101100219997 Mus musculus Ccr1 gene Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000001949 anaesthesia Methods 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000011685 brown norway rat Methods 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000031902 chemoattractant activity Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 2
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 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 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000001861 immunosuppressant effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000013425 morphometry Methods 0.000 description 2
- 230000002956 necrotizing effect Effects 0.000 description 2
- 238000013059 nephrectomy Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000002254 renal artery Anatomy 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- QRXMUCSWCMTJGU-UHFFFAOYSA-L (5-bromo-4-chloro-1h-indol-3-yl) phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP([O-])(=O)[O-])=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-L 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101710117545 C protein Proteins 0.000 description 1
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 102100034871 C-C motif chemokine 8 Human genes 0.000 description 1
- 101710155833 C-C motif chemokine 8 Proteins 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 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
- 241000282412 Homo Species 0.000 description 1
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 1
- 101000716070 Homo sapiens C-C chemokine receptor type 9 Proteins 0.000 description 1
- 101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- -1 IL-S Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101150069124 RAN1 gene Proteins 0.000 description 1
- 108020004518 RNA Probes Proteins 0.000 description 1
- 239000003391 RNA probe Substances 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101100355633 Salmo salar ran gene Proteins 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 102100035115 Testin Human genes 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 241001149964 Tolypocladium Species 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 description 1
- XNHJZNDJOUBNKB-QDEZUTFSSA-N [5-[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]-4,6-dioxononan-5-yl] dihydrogen phosphate Chemical compound P(=O)(O)(O)OC([C@@H]1[C@H]([C@H]([C@@H](O1)N1C=NC=2C(N)=NC=NC1=2)O)O)(C(CCC)=O)C(CCC)=O XNHJZNDJOUBNKB-QDEZUTFSSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000000961 alloantigen Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 238000011316 allogeneic transplantation Methods 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000294 dose-dependent toxicity Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 102000045341 human CCL5 Human genes 0.000 description 1
- 229960001067 hydrocortisone acetate Drugs 0.000 description 1
- 230000006028 immune-suppresssive effect Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000006759 inflammatory activation Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004924 lung microvascular endothelial cell Anatomy 0.000 description 1
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- FJQXCDYVZAHXNS-UHFFFAOYSA-N methadone hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 FJQXCDYVZAHXNS-UHFFFAOYSA-N 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 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
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 210000000512 proximal kidney tubule Anatomy 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002796 renal vein Anatomy 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 108091007551 scavenger receptor class L Proteins 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004926 tubular epithelial cell Anatomy 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 229950010342 uridine triphosphate Drugs 0.000 description 1
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000001631 vena cava inferior Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K38/19—Cytokines; Lymphokines; Interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/521—Chemokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98117697.7 | 1998-09-18 | ||
| EP98117697A EP1000626A1 (en) | 1998-09-18 | 1998-09-18 | Chemokine receptor antagonist and cyclosporin in combined therapy |
| PCT/EP1999/006844 WO2000016796A1 (en) | 1998-09-18 | 1999-09-16 | Chemokine receptor antagonist and cyclosporin in combined therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2344370A1 true CA2344370A1 (en) | 2000-03-30 |
Family
ID=8232654
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002344370A Abandoned CA2344370A1 (en) | 1998-09-18 | 1999-09-16 | Chemokine receptor antagonist and cyclosporin in combined therapy |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6902728B1 (enExample) |
| EP (2) | EP1000626A1 (enExample) |
| JP (1) | JP2003519082A (enExample) |
| KR (1) | KR100613950B1 (enExample) |
| CN (1) | CN1177613C (enExample) |
| AR (1) | AR021810A1 (enExample) |
| AT (1) | ATE227582T1 (enExample) |
| AU (1) | AU766595B2 (enExample) |
| BR (1) | BR9913846A (enExample) |
| CA (1) | CA2344370A1 (enExample) |
| DE (1) | DE69903964T2 (enExample) |
| DK (1) | DK1113811T3 (enExample) |
| EA (1) | EA003181B1 (enExample) |
| EE (1) | EE04705B1 (enExample) |
| ES (1) | ES2186411T3 (enExample) |
| HK (1) | HK1041225B (enExample) |
| IL (2) | IL141899A0 (enExample) |
| NO (1) | NO20011371L (enExample) |
| PT (1) | PT1113811E (enExample) |
| SI (1) | SI1113811T1 (enExample) |
| UA (1) | UA60379C2 (enExample) |
| WO (1) | WO2000016796A1 (enExample) |
| ZA (1) | ZA200101909B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7259136B2 (en) | 1999-04-30 | 2007-08-21 | Amylin Pharmaceuticals, Inc. | Compositions and methods for treating peripheral vascular disease |
| US6740636B2 (en) * | 2000-07-31 | 2004-05-25 | Schering Aktiengesellschaft | Non-peptide CCR1 receptor antagonists in combination with cyclosporin A for the treatment of heart transplant rejection |
| LT5132B (lt) | 2000-07-31 | 2004-05-25 | Schering Aktiengesellschaft | Nepeptidiniai ccr1 receptorių antagonistai derinyje su ciklosporinu a širdies transplanto atmetimui gydyti |
| EP2185719B1 (en) | 2007-08-02 | 2013-11-13 | NovImmune SA | Anti-rantes antibodies and methods of use thereof |
| WO2017040515A1 (en) * | 2015-08-31 | 2017-03-09 | Hitachi Chemical Co., Ltd. | Molecular methods for assessing post kidney transplant complications |
| JP6624704B2 (ja) | 2015-08-31 | 2019-12-25 | 日立化成株式会社 | 尿路上皮疾患の評価のための分子法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU221089B1 (en) * | 1994-12-08 | 2002-08-28 | Glaxo Group Ltd | Rantes peptide derivates with antagonistic effect and uses thereof |
| EP0845994A1 (en) * | 1995-08-09 | 1998-06-10 | Schering Corporation | Combined use of interleukin-10 and cyclosporin for immunosuppression therapy |
| US6184235B1 (en) * | 1996-08-14 | 2001-02-06 | Warner-Lambert Company | 2-phenyl benzimidazole derivatives as MCP-1 antagonists |
| WO1998006751A1 (en) * | 1996-08-16 | 1998-02-19 | Research Corporation Technologies, Inc. | Mcp-3, rantes and mip-1alpha receptor antagonists |
-
1998
- 1998-09-18 EP EP98117697A patent/EP1000626A1/en not_active Withdrawn
-
1999
- 1999-09-16 AR ARP990104655A patent/AR021810A1/es unknown
- 1999-09-16 ZA ZA200101909A patent/ZA200101909B/xx unknown
- 1999-09-16 CN CNB998111252A patent/CN1177613C/zh not_active Expired - Fee Related
- 1999-09-16 IL IL141899??A patent/IL141899A0/xx active IP Right Grant
- 1999-09-16 EP EP99948760A patent/EP1113811B1/en not_active Expired - Lifetime
- 1999-09-16 EA EA200100366A patent/EA003181B1/ru not_active IP Right Cessation
- 1999-09-16 SI SI9930157T patent/SI1113811T1/xx unknown
- 1999-09-16 WO PCT/EP1999/006844 patent/WO2000016796A1/en not_active Ceased
- 1999-09-16 DE DE69903964T patent/DE69903964T2/de not_active Expired - Lifetime
- 1999-09-16 ES ES99948760T patent/ES2186411T3/es not_active Expired - Lifetime
- 1999-09-16 HK HK02103034.0A patent/HK1041225B/zh not_active IP Right Cessation
- 1999-09-16 US US09/787,335 patent/US6902728B1/en not_active Expired - Fee Related
- 1999-09-16 DK DK99948760T patent/DK1113811T3/da active
- 1999-09-16 KR KR1020017003199A patent/KR100613950B1/ko not_active Expired - Fee Related
- 1999-09-16 AT AT99948760T patent/ATE227582T1/de active
- 1999-09-16 AU AU61914/99A patent/AU766595B2/en not_active Ceased
- 1999-09-16 CA CA002344370A patent/CA2344370A1/en not_active Abandoned
- 1999-09-16 PT PT99948760T patent/PT1113811E/pt unknown
- 1999-09-16 EE EEP200100159A patent/EE04705B1/xx not_active IP Right Cessation
- 1999-09-16 UA UA2001042570A patent/UA60379C2/uk unknown
- 1999-09-16 JP JP2000573757A patent/JP2003519082A/ja not_active Withdrawn
- 1999-09-16 BR BR9913846-8A patent/BR9913846A/pt not_active Application Discontinuation
-
2001
- 2001-03-08 IL IL141899A patent/IL141899A/en not_active IP Right Cessation
- 2001-03-16 NO NO20011371A patent/NO20011371L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| PT1113811E (pt) | 2003-03-31 |
| NO20011371D0 (no) | 2001-03-16 |
| US6902728B1 (en) | 2005-06-07 |
| EE04705B1 (et) | 2006-10-16 |
| AU6191499A (en) | 2000-04-10 |
| EA200100366A1 (ru) | 2001-08-27 |
| BR9913846A (pt) | 2001-06-05 |
| EP1000626A1 (en) | 2000-05-17 |
| DE69903964D1 (en) | 2002-12-19 |
| SI1113811T1 (en) | 2003-04-30 |
| KR100613950B1 (ko) | 2006-08-18 |
| EA003181B1 (ru) | 2003-02-27 |
| CN1177613C (zh) | 2004-12-01 |
| KR20010075060A (ko) | 2001-08-09 |
| JP2003519082A (ja) | 2003-06-17 |
| EE200100159A (et) | 2002-08-15 |
| DK1113811T3 (da) | 2003-03-10 |
| ZA200101909B (en) | 2001-09-11 |
| ATE227582T1 (de) | 2002-11-15 |
| CN1319021A (zh) | 2001-10-24 |
| EP1113811B1 (en) | 2002-11-13 |
| IL141899A0 (en) | 2002-03-10 |
| HK1041225B (zh) | 2005-04-22 |
| IL141899A (en) | 2007-12-03 |
| NO20011371L (no) | 2001-03-16 |
| AU766595B2 (en) | 2003-10-16 |
| AR021810A1 (es) | 2002-08-07 |
| ES2186411T3 (es) | 2003-05-01 |
| UA60379C2 (uk) | 2003-10-15 |
| WO2000016796A1 (en) | 2000-03-30 |
| DE69903964T2 (de) | 2003-03-27 |
| HK1041225A1 (en) | 2002-07-05 |
| EP1113811A1 (en) | 2001-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gröne et al. | Met‐RANTES reduces vascular and tubular damage during acute renal transplant rejection: blocking monocyte arrest and recruitment | |
| Rückert et al. | Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the pathogenesis of psoriasis? | |
| Yin et al. | SDF-1α involved in mobilization and recruitment of endothelial progenitor cells after arterial injury in mice | |
| Sano et al. | Cytokine expression during orthotopic corneal allograft rejection in mice. | |
| WO2001078708A1 (en) | Treating graft rejection with cxcr3 inhibitors | |
| Amersi et al. | Fibronectin-α4β1 integrin-mediated blockade protects genetically fat zucker rat livers from ischemia/reperfusion injury | |
| Suzuki et al. | Susceptibility to T cell-mediated injury in immune complex disease is linked to local activation of renin-angiotensin system: the role of NF-AT pathway | |
| Ruers et al. | Immunohistological observations in rat kidney allografts after local steroid administration. | |
| EP1113811B1 (en) | Chemokine receptor antagonist and cyclosporin in combined therapy | |
| US5675062A (en) | Cellular basis of transplant arteriosclerosis in mice | |
| Emanuelli et al. | Role of platelet activating factor in acute pancreatitis induced by lipopolysaccharides in rabbits | |
| EP2063908B1 (en) | Use of modified interleukin-8 proteins for treating reperfusion injury or transplant rejection | |
| WO2018137701A1 (zh) | 靶向cxcr7的药物组合物和方法 | |
| EP1671648A1 (en) | Prevention and treatment for gvhd | |
| MXPA01002838A (en) | Chemokine receptor antagonist and cyclosporin in combined therapy | |
| SHIRwAN et al. | Prevention of orthotopic liver allograft rejection in rats with a short-term brequinar sodium therapy: Analysis of intragraft cytokine gene expression | |
| Leeuwenberg et al. | Soluble tumor necrosis factor-receptors are not a useful marker of acute allograft rejection: a study in patients with renal or cardiac allografts | |
| AU2862300A (en) | Methods for preventing graft rejection and ischemia-reperfusion injury | |
| NISHIKAWA et al. | Tissue distribution of the guinea‐pig decay‐accelerating factor | |
| Okumura et al. | Susceptibility to T Cell-Mediated Injury in | |
| Żeglen et al. | sCD30, interleukin-1β-converting enzyme and anti-Annexin V autoantibodies concentrations in heart transplant recipients | |
| Shiao et al. | CHARACTERIZATION OF THE T CELLS THAT MEDIATE HUMAN MICROVASCULAR REJECTION | |
| Sager et al. | Expression of carcinoembryonic antigen–related cell adhesion molecule 1 in acute rejection of human renal allografts | |
| DiPirro | Studies on the involvement of tumor necrosis factor in the pathogenesis of the generalized Shwartzman reaction in the rabbit |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |