JP6621544B2 - Fstl1タンパク質を有効成分として含有する、癌または癌転移の予防及び治療用の薬学的組成物 - Google Patents
Fstl1タンパク質を有効成分として含有する、癌または癌転移の予防及び治療用の薬学的組成物 Download PDFInfo
- Publication number
- JP6621544B2 JP6621544B2 JP2018545791A JP2018545791A JP6621544B2 JP 6621544 B2 JP6621544 B2 JP 6621544B2 JP 2018545791 A JP2018545791 A JP 2018545791A JP 2018545791 A JP2018545791 A JP 2018545791A JP 6621544 B2 JP6621544 B2 JP 6621544B2
- Authority
- JP
- Japan
- Prior art keywords
- breast cancer
- fstl1
- protein
- metastasis
- active ingredient
- 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.)
- Expired - Fee Related
Links
- 101001062535 Homo sapiens Follistatin-related protein 1 Proteins 0.000 title claims description 102
- 102100029378 Follistatin-related protein 1 Human genes 0.000 title claims description 101
- 206010027476 Metastases Diseases 0.000 title claims description 54
- 230000009401 metastasis Effects 0.000 title claims description 52
- 239000004480 active ingredient Substances 0.000 title claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 17
- 206010028980 Neoplasm Diseases 0.000 title description 34
- 201000011510 cancer Diseases 0.000 title description 27
- 206010006187 Breast cancer Diseases 0.000 claims description 90
- 208000026310 Breast neoplasm Diseases 0.000 claims description 90
- 210000004027 cell Anatomy 0.000 claims description 76
- 108090000623 proteins and genes Proteins 0.000 claims description 43
- 239000013598 vector Substances 0.000 claims description 34
- 210000000988 bone and bone Anatomy 0.000 claims description 31
- 102000004169 proteins and genes Human genes 0.000 claims description 18
- 102000040430 polynucleotide Human genes 0.000 claims description 15
- 108091033319 polynucleotide Proteins 0.000 claims description 15
- 239000002157 polynucleotide Substances 0.000 claims description 15
- 230000002265 prevention Effects 0.000 claims description 11
- 235000013402 health food Nutrition 0.000 claims description 8
- 241001430294 unidentified retrovirus Species 0.000 claims description 8
- 241000700605 Viruses Species 0.000 claims description 4
- 210000004881 tumor cell Anatomy 0.000 claims description 4
- 241000701161 unidentified adenovirus Species 0.000 claims description 4
- 241000702421 Dependoparvovirus Species 0.000 claims description 3
- 241000700584 Simplexvirus Species 0.000 claims description 3
- 210000004443 dendritic cell Anatomy 0.000 claims description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 2
- 239000013603 viral vector Substances 0.000 claims description 2
- 241000713666 Lentivirus Species 0.000 claims 1
- 239000013612 plasmid Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 description 30
- 108010057466 NF-kappa B Proteins 0.000 description 28
- 102000003945 NF-kappa B Human genes 0.000 description 28
- 230000014509 gene expression Effects 0.000 description 26
- 102100023132 Transcription factor Jun Human genes 0.000 description 24
- 108010018242 Transcription Factor AP-1 Proteins 0.000 description 21
- 210000002997 osteoclast Anatomy 0.000 description 16
- 239000000203 mixture Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 12
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 12
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 12
- 230000001105 regulatory effect Effects 0.000 description 12
- 230000019491 signal transduction Effects 0.000 description 12
- 238000010171 animal model Methods 0.000 description 11
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 10
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 10
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 10
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 10
- 238000012790 confirmation Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
- 230000005907 cancer growth Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000001629 suppression Effects 0.000 description 8
- 102000010498 Receptor Activator of Nuclear Factor-kappa B Human genes 0.000 description 7
- 108010038036 Receptor Activator of Nuclear Factor-kappa B Proteins 0.000 description 7
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 7
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 5
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000009545 invasion Effects 0.000 description 5
- 238000011580 nude mouse model Methods 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 4
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 4
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 4
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 210000002798 bone marrow cell Anatomy 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 230000005748 tumor development Effects 0.000 description 4
- 239000000225 tumor suppressor protein Substances 0.000 description 4
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 230000004568 DNA-binding Effects 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 101150001032 FSTL1 gene Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 3
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 3
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108091007960 PI3Ks Proteins 0.000 description 3
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 3
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 3
- 101150045355 akt1 gene Proteins 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000003636 conditioned culture medium Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 210000002303 tibia Anatomy 0.000 description 3
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 230000005760 tumorsuppression Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108060006678 I-kappa-B kinase Proteins 0.000 description 2
- 102000001284 I-kappa-B kinase Human genes 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000018745 NF-KappaB Inhibitor alpha Human genes 0.000 description 2
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 102000008108 Osteoprotegerin Human genes 0.000 description 2
- 108010035042 Osteoprotegerin Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 230000004712 cancer cell adhesion Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010874 in vitro model Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
- 229940096397 interleukin-8 Drugs 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- XXUPLYBCNPLTIW-UHFFFAOYSA-N octadec-7-ynoic acid Chemical compound CCCCCCCCCCC#CCCCCCC(O)=O XXUPLYBCNPLTIW-UHFFFAOYSA-N 0.000 description 2
- 210000000963 osteoblast Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000003197 protein kinase B inhibitor Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000003757 reverse transcription PCR 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
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- XUHRVZXFBWDCFB-QRTDKPMLSA-N (3R)-4-[[(3S,6S,9S,12R,15S,18R,21R,24R,27R,28R)-12-(3-amino-3-oxopropyl)-6-[(2S)-butan-2-yl]-3-(2-carboxyethyl)-18-(hydroxymethyl)-28-methyl-9,15,21,24-tetrakis(2-methylpropyl)-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octazacyclooctacos-27-yl]amino]-3-[[(2R)-2-[[(3S)-3-hydroxydecanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoic acid Chemical compound CCCCCCC[C@H](O)CC(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H]1[C@@H](C)OC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CO)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC1=O)[C@@H](C)CC XUHRVZXFBWDCFB-QRTDKPMLSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 229940126638 Akt inhibitor Drugs 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102100029379 Follistatin-related protein 3 Human genes 0.000 description 1
- 101710160621 Fusion glycoprotein F0 Proteins 0.000 description 1
- 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 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001062529 Homo sapiens Follistatin-related protein 3 Proteins 0.000 description 1
- 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 206010027452 Metastases to bone Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 229940116355 PI3 kinase inhibitor Drugs 0.000 description 1
- 239000012828 PI3K inhibitor Substances 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010061902 Pancreatic neoplasm 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
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000014128 RANK Ligand Human genes 0.000 description 1
- 108010025832 RANK Ligand Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102100024547 Tensin-1 Human genes 0.000 description 1
- 108010088950 Tensins Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 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 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 235000005523 excessive nutrition Nutrition 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002608 insulinlike Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000020395 negative regulation of osteoclast differentiation Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 230000000010 osteolytic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 210000004417 patella Anatomy 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 1
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000575 proteomic method Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000012121 regulation of immune response Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000002100 tumorsuppressive effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000007805 zymography Methods 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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- A61K38/1741—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals alpha-Glycoproteins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/18—Peptides; Protein hydrolysates
-
- 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
-
- 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
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- 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
- G01N33/502—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 non-proliferative effects
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Marine Sciences & Fisheries (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Analytical Chemistry (AREA)
Description
本発明に用いられた人体乳癌細胞(MDA−MB−231 cell)及び前立腺癌細胞(PC−3M cells)は、アメリカン・タイプ・カルチャー・コレクション(ATCC;Rockville、MD、USA)から購入した。細胞は、湿潤な5%CO2、37℃の培養器でダルベッコ変法イーグル培地/Nutrient Mixture Ham's F12(DMEM/F12、Gibco/BRL.Gaithersburg、MD、USA)、10%FBS、100units/mlのペニシリン、100μg/mLのストレプトマイシン(Gibco/BRL)が含まれるように細胞培養液を製造して培養した。細胞数(すなわち、Cell density)が10cm培養皿の80〜90%程度に達した時、リン酸緩衝生理食塩水溶液(Phosphatate Buffered Saline solution;PBS)で2回洗い流し、Trypsin−EDTA(Gibco/BRL)を処理して細胞を継代培養するか、或いはin vivoまたはin vitro実験のためにサンプルを用意し、細胞培養液は、2〜3日ごとに交換した。
癌の成長及び転移と関連性があると知られている転写因子AP−1、そしてFSTL1による細胞内の遺伝子変化パターンを分析するために、c−jun/AP−1の優性ネガティブ突然変異(Dominant−Negative Mutant)遺伝子またはFSTL1クローンをレトロウイルスで形質導入されたそれぞれのMDA−MB−231乳癌細胞株において発現が増加または減少する媒介遺伝子群(すなわち、Gene pool)を、ノーザンブロット法及びcDNAマイクロアレイ分析(すなわち、Human genome−U133Plus2.0genechip、Affymetrix社製を使用)によって確認した。
FSTL1の抗癌活性信号経路を確認するために、前記<実施例1>で培養した乳癌細胞(MDA−MB−231 cell)、前立腺癌細胞(PC−3M)または対照群として空レトロウイルス(retrovirus)で形質導入されたMDA−MB−231乳癌細胞株(MDA/C)に、FSTL1コンディション培地(5%、v/v)及び、Akt信号伝逹体系の活性因子であるIGF−1(insulin−like factor−1)100ng/mlを処理した後、Akt1及びPTEN(phosphatase and tensin homolog deleted on chromosome10)活性を、ウエスタンブロットを用いて確認した。一方、対照薬物としては、PI−3K(phosphatidylinositol−3 kinase)抑制剤またはAkt抑制剤であるLY294002を用いた。
FSTL1のNF−κB信号経路を確認するために、まずは、Human Genome−U133Plus2.0Genechip、Affymetrixを用い、FSTL1によって遺伝子発現が下方調節された遺伝子を分析した。
FSTL1−媒介の様々な分子(MMP−9、VEGF、ICAM−1)の発現を分析した。前記分子は、NF−κBによって調節されるものであり、転移に関する浸潤(invasion)、血管新生及び細胞付着に関する。特に、MMP−9は、腫瘍血管新生及び転移のみならず、乳癌の活性を促す癌に必要な成長因子の活性に関するものである。それに、MMP−9は、破骨細胞によって発現され、破骨細胞の移動(migration)に必要である。よって、MMP−9は、骨吸収に関する破骨細胞微細環境において重要な役割を果たす。
<4−1> 実験動物の用意
ヌードマウスは、BALB/c/nu(Korea Research Institute of Bioscience and Biotechnology、Korea)を基本種とし、20匹のいずれも生後6〜8週、体重が約20gの雌のみを用いた。滅菌消毒されたマウスケージで滅菌された水及び飼料を供給し、層流(lamina flow)を持続的に維持したクリーンベンチの中に置くことで清浄な環境を維持し、すべての術式もまた、クリーンベンチの中で施した。ヌードマウスの昼夜間の生物学的サイクルのために、室内灯を12時間にかけて照影し、12時間にかけて点滅した。
前記実験例<4−1>で用意したヌードマウスに、前記<実施例2>で用意したFSTL1を発現する乳癌細胞株を、1ccの注射器及び25ゲージの注射針を用いてヌードマウスの背中に皮下注射接種した後、対照群の乳癌細胞株を移植したヌードマウスと腫瘍の体積を測定した。腫瘍の体積は、長さ及び幅をカリパスで3日に一回ずつ測定し、Gutmanなどが提案した方法の公式によって腫瘍の体積を算出した。
図5Bに示したように、本発明のFSTL1は、骨転移を約67%以上抑制することが確認された(図5B)。
<5−1> マウス骨髄細胞の培養
ICRマウス(6〜9週、雄)を頚椎脱骨した後、70%のエタノールで消毒した。脛骨部分の肌を切開して付着筋肉を剥離した。脛骨遠心部を切断して膝蓋骨を脱骨させることで脛骨を摘出した。骨の両端を僅かに切って一方の端に25Gの注射針をさし、α−MEMを流して骨髄細胞を試験管に集めた。遠心分離した後、α−MEMに懸濁して2倍のGey's solutionを加えることで赤血球を除去した。遠心分離した後、10%のFBSが含有されたα−MEMで再懸濁した。
前記<5−1>で培養した骨髄細胞を、96のウェルプレートに1×103個で接種した。それから、本発明のFSTL1のCMを前処理した後、ランクリガンドを処理して5%CO2のインキュベーターで培養してから7日後、破骨細胞をよく観察できるようにTRAP(tartrate resistance acid phosphatase)染色法を用いて染色した後、破骨細胞に分化された細胞の数を計数することで、FSTL1のCMの破骨細胞分化の抑制程度を確認した。
Claims (9)
- FSTL1(Follistatin−like1)タンパク質を有効成分として含有する、乳癌または乳癌転移の予防及び治療用の薬学的組成物。
- FSTL1タンパク質を暗号化するポリヌクレオチドを含むベクター、前記ベクターを含む細胞またはそれの培養液を有効成分として含有する、乳癌または乳癌転移の予防及び治療用の薬学的組成物。
- 前記ベクターが、直鎖状DNA、プラスミドDNAまたは組換えウイルス性ベクターであることを特徴とする、請求項2に記載の乳癌または乳癌転移の予防及び治療用の薬学的組成物。
- 前記組換えウイルスが、レトロウイルス、アデノウイルス、アデノ随伴ウイルス、単純ヘルペスウィルス、及びレンチウイルスで構成される群から選択されるいずれか一種であることを特徴とする、請求項3に記載の乳癌または乳癌転移の予防及び治療用の薬学的組成物。
- 前記細胞が、造血幹細胞、樹状細胞、自己腫瘍細胞(autologous tumor cells)及び定着腫瘍細胞(established tumor cells)で構成される群から選択されるいずれか一種であることを特徴とする、請求項2に記載の乳癌または乳癌転移の予防及び治療用の薬学的組成物。
- FSTL1タンパク質を有効成分として含有する、乳癌または乳癌転移の予防及び改善用の健康食品。
- FSTL1(Follistatin−like1)タンパク質を有効成分として含有する、乳癌骨転移の予防及び治療用の薬学的組成物。
- FSTL1タンパク質を暗号化するポリヌクレオチドを含むベクター、前記ベクターを含む細胞またはそれの培養液を有効成分として含有する、乳癌骨転移の予防及び治療用の薬学的組成物。
- FSTL1タンパク質を有効成分として含有する、乳癌骨転移の予防及び改善用の健康食品。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020150161900A KR101804246B1 (ko) | 2015-11-18 | 2015-11-18 | Fstl1 단백질을 유효성분으로 함유하는 골대사성 질환 예방 및 치료용 약학적 조성물 |
KR10-2015-0161900 | 2015-11-18 | ||
PCT/KR2016/013358 WO2017086744A1 (ko) | 2015-11-18 | 2016-11-18 | Fstl1 단백질을 유효성분으로 함유하는 암 또는 암전이 예방 및 치료용 약학적 조성물 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018536032A JP2018536032A (ja) | 2018-12-06 |
JP6621544B2 true JP6621544B2 (ja) | 2019-12-18 |
Family
ID=58719224
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018545791A Expired - Fee Related JP6621544B2 (ja) | 2015-11-18 | 2016-11-18 | Fstl1タンパク質を有効成分として含有する、癌または癌転移の予防及び治療用の薬学的組成物 |
Country Status (6)
Country | Link |
---|---|
US (1) | US20190076503A1 (ja) |
EP (1) | EP3398608A4 (ja) |
JP (1) | JP6621544B2 (ja) |
KR (1) | KR101804246B1 (ja) |
CN (1) | CN108778313A (ja) |
WO (1) | WO2017086744A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102393730B1 (ko) | 2019-12-18 | 2022-05-04 | 경북대학교 산학협력단 | Fstl1을 유효성분으로 함유하는 골 충진용 조성물 |
JP2023535280A (ja) * | 2020-07-20 | 2023-08-17 | エフエヌシーティー バイオテック、インコーポレイテッド | 大腸癌転移阻害剤をスクリーニングする方法 |
CN111643514B (zh) * | 2020-07-27 | 2023-10-27 | 济宁市第一人民医院 | 一种治疗前列腺癌药物的制备方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005000087A2 (en) * | 2003-06-03 | 2005-01-06 | Chiron Corporation | Gene products differentially expressed in cancerous colon cells and their methods of use ii |
EP2561887B8 (en) | 2003-01-14 | 2016-12-21 | Dana-Farber Cancer Institute, Inc. | Cancer therapy sensitizer |
WO2009097424A1 (en) * | 2008-01-29 | 2009-08-06 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Fstl-1 as a biomarker of inflammation |
-
2015
- 2015-11-18 KR KR1020150161900A patent/KR101804246B1/ko active IP Right Grant
-
2016
- 2016-11-18 WO PCT/KR2016/013358 patent/WO2017086744A1/ko active Application Filing
- 2016-11-18 CN CN201680079698.8A patent/CN108778313A/zh active Pending
- 2016-11-18 EP EP16866696.4A patent/EP3398608A4/en not_active Withdrawn
- 2016-11-18 JP JP2018545791A patent/JP6621544B2/ja not_active Expired - Fee Related
- 2016-11-18 US US15/777,497 patent/US20190076503A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP3398608A1 (en) | 2018-11-07 |
CN108778313A (zh) | 2018-11-09 |
EP3398608A4 (en) | 2020-01-01 |
KR20170058104A (ko) | 2017-05-26 |
US20190076503A1 (en) | 2019-03-14 |
WO2017086744A1 (ko) | 2017-05-26 |
JP2018536032A (ja) | 2018-12-06 |
KR101804246B1 (ko) | 2017-12-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Swiatek-Machado et al. | STAT signaling in glioma cells | |
Monsalve et al. | Notch-1 up-regulation and signaling following macrophage activation modulates gene expression patterns known to affect antigen-presenting capacity and cytotoxic activity | |
WO2009017274A1 (en) | An agent for differentiating hematopoietic stem cell into natural killer cell comprising yc-1 or il-21 and a method of differentiating hematopoietic stem cell into natural killer cell using thereof | |
KR19990071523A (ko) | Il-8 및 il-8 수용체에 대한 안티센스올리고누클레오티드에 의한 종양 성장의 억제방법 | |
JP6621544B2 (ja) | Fstl1タンパク質を有効成分として含有する、癌または癌転移の予防及び治療用の薬学的組成物 | |
Stalin et al. | Inhibition of host NOX1 blocks tumor growth and enhances checkpoint inhibitor–based immunotherapy | |
Fons et al. | Tumor vasculature is regulated by FGF/FGFR signaling‐mediated angiogenesis and bone marrow‐derived cell recruitment: this mechanism is inhibited by SSR128129E, the first allosteric antagonist of FGFRs | |
US10166203B2 (en) | Pharmaceutical composition for treating cancer including 2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol as active ingredient | |
Lin et al. | Simvastatin suppresses osteoblastic expression of Cyr61 and progression of apical periodontitis through enhancement of the transcription factor Forkhead/winged helix box protein O3a | |
Kalechman et al. | Inhibition of interleukin-10 by the immunomodulator AS101 reduces mesangial cell proliferation in experimental mesangioproliferative glomerulonephritis: association with dephosphorylation of STAT3 | |
CN114870009A (zh) | 一种抗肿瘤联合组合物及其应用和抗肿瘤药物 | |
Shouda et al. | Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells | |
Moretti et al. | Activation of the orphan nuclear receptor RORα induces growth arrest in androgen‐independent DU 145 prostate cancer cells | |
KR101723786B1 (ko) | Il―21을 발현하는 중간엽 줄기세포를 포함하는 b 세포 림프종 예방 또는 치료용 조성물 | |
Yen Chong et al. | Cell cycle effects of IL-10 on malignant B-1 cells | |
KR20050103259A (ko) | 인터루킨-2 및 모노아세틸디글리세라이드-3을유효성분으로 함유하는 항암제 | |
CN114010789B (zh) | 蟾蜍甾烯类化合物在制备治疗egfr和/或stat3驱动疾病的药物中的应用 | |
KR101804248B1 (ko) | Fstl1 단백질을 유효성분으로 함유하는 암 예방 및 치료용 약학적 조성물 | |
KR101804241B1 (ko) | Fstl1 단백질을 유효성분으로 함유하는 암전이 예방 및 치료용 약학적 조성물 | |
KR101928496B1 (ko) | Fstl1 단백질을 이용한 암 또는 암 전이 치료제 스크리닝 방법 | |
Yakes et al. | CM101 treatment overrides tumor-induced immunoprivilege leading to apoptosis | |
JP2019516803A (ja) | 医薬組成物及び自己免疫疾患の治療におけるその使用 | |
KR101514521B1 (ko) | X형 구조의 dna를 유효 성분으로 포함하는 면역 효과 및 항암 효과 증진용 조성물 | |
US20110046223A1 (en) | Treatment of neurofibromatosis | |
KR20090125246A (ko) | 전신성 에리테마토데스의 예방 및/또는 치료제 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180718 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180718 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20181102 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20181102 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190604 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190904 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20191105 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20191119 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6621544 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |