JP7510634B2 - エキソソームの産生及びその使用 - Google Patents
エキソソームの産生及びその使用 Download PDFInfo
- Publication number
- JP7510634B2 JP7510634B2 JP2022193265A JP2022193265A JP7510634B2 JP 7510634 B2 JP7510634 B2 JP 7510634B2 JP 2022193265 A JP2022193265 A JP 2022193265A JP 2022193265 A JP2022193265 A JP 2022193265A JP 7510634 B2 JP7510634 B2 JP 7510634B2
- Authority
- JP
- Japan
- Prior art keywords
- cancer
- cells
- protein
- exosome
- exosomes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 210000001808 exosome Anatomy 0.000 title claims description 176
- 238000004519 manufacturing process Methods 0.000 title description 9
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 72
- 206010028980 Neoplasm Diseases 0.000 claims description 66
- 102000004169 proteins and genes Human genes 0.000 claims description 58
- 108090000623 proteins and genes Proteins 0.000 claims description 58
- 201000011510 cancer Diseases 0.000 claims description 47
- 108020001507 fusion proteins Proteins 0.000 claims description 41
- 102000037865 fusion proteins Human genes 0.000 claims description 41
- 229960004679 doxorubicin Drugs 0.000 claims description 34
- 102000035160 transmembrane proteins Human genes 0.000 claims description 28
- 108091005703 transmembrane proteins Proteins 0.000 claims description 28
- 239000002246 antineoplastic agent Substances 0.000 claims description 27
- 102100025222 CD63 antigen Human genes 0.000 claims description 24
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 22
- 230000001225 therapeutic effect Effects 0.000 claims description 20
- 239000002679 microRNA Substances 0.000 claims description 17
- 102100027221 CD81 antigen Human genes 0.000 claims description 16
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 claims description 16
- 102100037904 CD9 antigen Human genes 0.000 claims description 15
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 claims description 15
- 229940127089 cytotoxic agent Drugs 0.000 claims description 15
- 229940079593 drug Drugs 0.000 claims description 15
- 206010006187 Breast cancer Diseases 0.000 claims description 13
- 208000026310 Breast neoplasm Diseases 0.000 claims description 13
- 108091029119 miR-34a stem-loop Proteins 0.000 claims description 13
- 108700011259 MicroRNAs Proteins 0.000 claims description 9
- 206010005003 Bladder cancer Diseases 0.000 claims description 7
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 7
- 201000007270 liver cancer Diseases 0.000 claims description 7
- 208000014018 liver neoplasm Diseases 0.000 claims description 7
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 7
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 6
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 6
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 6
- 229960004316 cisplatin Drugs 0.000 claims description 6
- 229960004397 cyclophosphamide Drugs 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 208000000172 Medulloblastoma Diseases 0.000 claims description 5
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 229960004562 carboplatin Drugs 0.000 claims description 5
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 5
- 229960005277 gemcitabine Drugs 0.000 claims description 5
- 208000005017 glioblastoma Diseases 0.000 claims description 5
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
- 201000002528 pancreatic cancer Diseases 0.000 claims description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
- 229940063683 taxotere Drugs 0.000 claims description 5
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 4
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 4
- 229960001904 epirubicin Drugs 0.000 claims description 4
- 229960005079 pemetrexed Drugs 0.000 claims description 4
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims description 4
- 229940041181 antineoplastic drug Drugs 0.000 claims description 3
- 229940022353 herceptin Drugs 0.000 claims description 3
- 229960002087 pertuzumab Drugs 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 190000008236 carboplatin Chemical compound 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 196
- 239000000463 material Substances 0.000 description 52
- 125000004122 cyclic group Chemical group 0.000 description 46
- 238000000034 method Methods 0.000 description 29
- 230000012010 growth Effects 0.000 description 21
- 108700038175 YAP-Signaling Proteins Proteins 0.000 description 19
- 108091033319 polynucleotide Proteins 0.000 description 18
- 102000040430 polynucleotide Human genes 0.000 description 18
- 239000002157 polynucleotide Substances 0.000 description 18
- 239000002861 polymer material Substances 0.000 description 17
- 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 16
- 239000002953 phosphate buffered saline Substances 0.000 description 16
- -1 Alix Proteins 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 239000000017 hydrogel Substances 0.000 description 14
- 230000000638 stimulation Effects 0.000 description 14
- 239000001963 growth medium Substances 0.000 description 13
- 108091070501 miRNA Proteins 0.000 description 13
- 229920000249 biocompatible polymer Polymers 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 230000006870 function Effects 0.000 description 11
- 108700004892 gelatin methacryloyl Proteins 0.000 description 10
- 239000011148 porous material Substances 0.000 description 10
- 230000008685 targeting Effects 0.000 description 10
- 230000003013 cytotoxicity Effects 0.000 description 9
- 231100000135 cytotoxicity Toxicity 0.000 description 9
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 210000002889 endothelial cell Anatomy 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 230000028327 secretion Effects 0.000 description 8
- 102000007469 Actins Human genes 0.000 description 7
- 108010085238 Actins Proteins 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 239000013600 plasmid vector Substances 0.000 description 7
- 230000001737 promoting effect Effects 0.000 description 7
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 6
- 108010024164 HLA-G Antigens Proteins 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 238000004520 electroporation Methods 0.000 description 6
- 239000007850 fluorescent dye Substances 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 230000003068 static effect Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 239000013603 viral vector Substances 0.000 description 6
- 239000000090 biomarker Substances 0.000 description 5
- 210000000481 breast Anatomy 0.000 description 5
- 230000003833 cell viability Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000009295 crossflow filtration Methods 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 230000001603 reducing effect Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 102100025390 Integrin beta-2 Human genes 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 102000004243 Tubulin Human genes 0.000 description 4
- 108090000704 Tubulin Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 4
- 208000036815 beta tubulin Diseases 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 150000007523 nucleic acids Chemical group 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N verteporfin Chemical compound C=1C([C@@]2([C@H](C(=O)OC)C(=CC=C22)C(=O)OC)C)=NC2=CC(C(=C2C=C)C)=NC2=CC(C(=C2CCC(O)=O)C)=NC2=CC2=NC=1C(C)=C2CCC(=O)OC ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N 0.000 description 4
- 229960003895 verteporfin Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 3
- NMARPFMJVCXSAV-UHFFFAOYSA-N 5-[(3,5-diethoxy-4-pyrrol-1-ylphenyl)methyl]pyrimidine-2,4-diamine Chemical compound C=1C(OCC)=C(N2C=CC=C2)C(OCC)=CC=1CC1=CN=C(N)N=C1N NMARPFMJVCXSAV-UHFFFAOYSA-N 0.000 description 3
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 description 3
- 102100027217 CD82 antigen Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000914469 Homo sapiens CD82 antigen Proteins 0.000 description 3
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 description 3
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 3
- 102100032818 Integrin alpha-4 Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 102100033344 Programmed cell death 6-interacting protein Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000005907 cancer growth Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 238000011031 large-scale manufacturing process Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 3
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 210000002826 placenta Anatomy 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000004114 suspension culture Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 241000251468 Actinopterygii Species 0.000 description 2
- 239000012099 Alexa Fluor family Substances 0.000 description 2
- 102100026444 Arrestin domain-containing protein 1 Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 101000836492 Dictyostelium discoideum ALG-2 interacting protein X Proteins 0.000 description 2
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 2
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 2
- 101000785762 Homo sapiens Arrestin domain-containing protein 1 Proteins 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 2
- 101001134621 Homo sapiens Programmed cell death 6-interacting protein Proteins 0.000 description 2
- 101000613251 Homo sapiens Tumor susceptibility gene 101 protein Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 108091028684 Mir-145 Proteins 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 2
- 102100035721 Syndecan-1 Human genes 0.000 description 2
- 102100026087 Syndecan-2 Human genes 0.000 description 2
- 108010083130 Syntenins Proteins 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 102100040879 Tumor susceptibility gene 101 protein Human genes 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000004115 adherent culture Methods 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 238000002669 amniocentesis Methods 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000005880 cancer cell killing Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000004624 confocal microscopy Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 229940103064 lipodox Drugs 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000005073 lymphatic endothelial cell Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 2
- 108091074450 miR-200c stem-loop Proteins 0.000 description 2
- 108091062762 miR-21 stem-loop Proteins 0.000 description 2
- 108091043187 miR-30a stem-loop Proteins 0.000 description 2
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 201000002740 oral squamous cell carcinoma Diseases 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920001992 poloxamer 407 Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000007639 printing Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 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 2
- 238000004627 transmission electron microscopy Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000012447 xenograft mouse model Methods 0.000 description 2
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
- BSDCIRGNJKZPFV-GWOFURMSSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-(2,5,6-trichlorobenzimidazol-1-yl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=CC(Cl)=C(Cl)C=C2N=C1Cl BSDCIRGNJKZPFV-GWOFURMSSA-N 0.000 description 1
- OOIBFPKQHULHSQ-UHFFFAOYSA-N (3-hydroxy-1-adamantyl) 2-methylprop-2-enoate Chemical compound C1C(C2)CC3CC2(O)CC1(OC(=O)C(=C)C)C3 OOIBFPKQHULHSQ-UHFFFAOYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- 238000012604 3D cell culture Methods 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 101710159080 Aconitate hydratase A Proteins 0.000 description 1
- 101710159078 Aconitate hydratase B Proteins 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 102100040026 Agrin Human genes 0.000 description 1
- 102100022749 Aminopeptidase N Human genes 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 229940088872 Apoptosis inhibitor Drugs 0.000 description 1
- 101100165655 Arabidopsis thaliana BRO1 gene Proteins 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 102100036597 Basement membrane-specific heparan sulfate proteoglycan core protein Human genes 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 102100035893 CD151 antigen Human genes 0.000 description 1
- 108010045374 CD36 Antigens Proteins 0.000 description 1
- 102000053028 CD36 Antigens Human genes 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 108010040467 CRISPR-Associated Proteins Proteins 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102100031519 Collagen alpha-1(VI) chain Human genes 0.000 description 1
- 102100025680 Complement decay-accelerating factor Human genes 0.000 description 1
- 101100117177 Coxiella burnetii (strain RSA 493 / Nine Mile phase I) dnaK gene Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 102100036462 Delta-like protein 1 Human genes 0.000 description 1
- 102100033553 Delta-like protein 4 Human genes 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102100032790 Flotillin-1 Human genes 0.000 description 1
- 102100023513 Flotillin-2 Human genes 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 102100040510 Galectin-3-binding protein Human genes 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 102100030651 Glutamate receptor 2 Human genes 0.000 description 1
- 102100030669 Glutamate receptor 3 Human genes 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102100035716 Glycophorin-A Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000959594 Homo sapiens Agrin Proteins 0.000 description 1
- 101000757160 Homo sapiens Aminopeptidase N Proteins 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101001000001 Homo sapiens Basement membrane-specific heparan sulfate proteoglycan core protein Proteins 0.000 description 1
- 101000946874 Homo sapiens CD151 antigen Proteins 0.000 description 1
- 101000941581 Homo sapiens Collagen alpha-1(VI) chain Proteins 0.000 description 1
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 description 1
- 101000928537 Homo sapiens Delta-like protein 1 Proteins 0.000 description 1
- 101000872077 Homo sapiens Delta-like protein 4 Proteins 0.000 description 1
- 101000847538 Homo sapiens Flotillin-1 Proteins 0.000 description 1
- 101000828609 Homo sapiens Flotillin-2 Proteins 0.000 description 1
- 101000967904 Homo sapiens Galectin-3-binding protein Proteins 0.000 description 1
- 101001010449 Homo sapiens Glutamate receptor 2 Proteins 0.000 description 1
- 101001010434 Homo sapiens Glutamate receptor 3 Proteins 0.000 description 1
- 101001074244 Homo sapiens Glycophorin-A Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101001078133 Homo sapiens Integrin alpha-2 Proteins 0.000 description 1
- 101000994378 Homo sapiens Integrin alpha-3 Proteins 0.000 description 1
- 101000994369 Homo sapiens Integrin alpha-5 Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101001046677 Homo sapiens Integrin alpha-V Proteins 0.000 description 1
- 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 description 1
- 101001015006 Homo sapiens Integrin beta-4 Proteins 0.000 description 1
- 101001015059 Homo sapiens Integrin beta-5 Proteins 0.000 description 1
- 101001015064 Homo sapiens Integrin beta-6 Proteins 0.000 description 1
- 101001015037 Homo sapiens Integrin beta-7 Proteins 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 101000599858 Homo sapiens Intercellular adhesion molecule 2 Proteins 0.000 description 1
- 101000599862 Homo sapiens Intercellular adhesion molecule 3 Proteins 0.000 description 1
- 101001034314 Homo sapiens Lactadherin Proteins 0.000 description 1
- 101001008568 Homo sapiens Laminin subunit beta-1 Proteins 0.000 description 1
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 description 1
- 101000980823 Homo sapiens Leukocyte surface antigen CD53 Proteins 0.000 description 1
- 101000634835 Homo sapiens M1-specific T cell receptor alpha chain Proteins 0.000 description 1
- 101000763322 Homo sapiens M1-specific T cell receptor beta chain Proteins 0.000 description 1
- 101001023043 Homo sapiens Myoblast determination protein 1 Proteins 0.000 description 1
- 101100082597 Homo sapiens PDCD6IP gene Proteins 0.000 description 1
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 description 1
- 101000994437 Homo sapiens Protein jagged-1 Proteins 0.000 description 1
- 101000994434 Homo sapiens Protein jagged-2 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101000651890 Homo sapiens Slit homolog 2 protein Proteins 0.000 description 1
- 101000651893 Homo sapiens Slit homolog 3 protein Proteins 0.000 description 1
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 1
- 101000692109 Homo sapiens Syndecan-2 Proteins 0.000 description 1
- 101000642688 Homo sapiens Syntaxin-3 Proteins 0.000 description 1
- 101000634836 Homo sapiens T cell receptor alpha chain MC.7.G5 Proteins 0.000 description 1
- 101000763321 Homo sapiens T cell receptor beta chain MC.7.G5 Proteins 0.000 description 1
- 101000759889 Homo sapiens Tetraspanin-14 Proteins 0.000 description 1
- 101000612838 Homo sapiens Tetraspanin-7 Proteins 0.000 description 1
- 101000847107 Homo sapiens Tetraspanin-8 Proteins 0.000 description 1
- 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000621459 Homo sapiens Vesicle transport through interaction with t-SNAREs homolog 1A Proteins 0.000 description 1
- 101000621456 Homo sapiens Vesicle transport through interaction with t-SNAREs homolog 1B 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
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 102100025305 Integrin alpha-2 Human genes 0.000 description 1
- 102100032819 Integrin alpha-3 Human genes 0.000 description 1
- 102100032817 Integrin alpha-5 Human genes 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 102100032999 Integrin beta-3 Human genes 0.000 description 1
- 102100033000 Integrin beta-4 Human genes 0.000 description 1
- 102100033010 Integrin beta-5 Human genes 0.000 description 1
- 102100033011 Integrin beta-6 Human genes 0.000 description 1
- 102100033016 Integrin beta-7 Human genes 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 102100037872 Intercellular adhesion molecule 2 Human genes 0.000 description 1
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 102100039648 Lactadherin Human genes 0.000 description 1
- 102100027448 Laminin subunit beta-1 Human genes 0.000 description 1
- 102100034710 Laminin subunit gamma-1 Human genes 0.000 description 1
- 101000839464 Leishmania braziliensis Heat shock 70 kDa protein Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 description 1
- 102100024221 Leukocyte surface antigen CD53 Human genes 0.000 description 1
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 1
- 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 108091028049 Mir-221 microRNA Proteins 0.000 description 1
- 108091093189 Mir-375 Proteins 0.000 description 1
- 108091080995 Mir-9/mir-79 microRNA precursor family Proteins 0.000 description 1
- 241000711408 Murine respirovirus Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 102100035077 Myoblast determination protein 1 Human genes 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 108010012255 Neural Cell Adhesion Molecule L1 Proteins 0.000 description 1
- 102100024964 Neural cell adhesion molecule L1 Human genes 0.000 description 1
- 102000001759 Notch1 Receptor Human genes 0.000 description 1
- 108010029755 Notch1 Receptor Proteins 0.000 description 1
- 102000001756 Notch2 Receptor Human genes 0.000 description 1
- 108010029751 Notch2 Receptor Proteins 0.000 description 1
- 102000001760 Notch3 Receptor Human genes 0.000 description 1
- 108010029756 Notch3 Receptor Proteins 0.000 description 1
- 102000001753 Notch4 Receptor Human genes 0.000 description 1
- 108010029741 Notch4 Receptor Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 101710149632 Pectinesterase A Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 108010009711 Phalloidine Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100040120 Prominin-1 Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102100032702 Protein jagged-1 Human genes 0.000 description 1
- 102100032733 Protein jagged-2 Human genes 0.000 description 1
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 1
- 101710105008 RNA-binding protein Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 102100027340 Slit homolog 2 protein Human genes 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108090000058 Syndecan-1 Proteins 0.000 description 1
- 108090000054 Syndecan-2 Proteins 0.000 description 1
- 102100026084 Syndecan-3 Human genes 0.000 description 1
- 108090000068 Syndecan-3 Proteins 0.000 description 1
- 102100037220 Syndecan-4 Human genes 0.000 description 1
- 108010055215 Syndecan-4 Proteins 0.000 description 1
- 102100035937 Syntaxin-3 Human genes 0.000 description 1
- 102100037225 Syntenin-2 Human genes 0.000 description 1
- 102000006276 Syntenins Human genes 0.000 description 1
- 102100029454 T cell receptor alpha chain MC.7.G5 Human genes 0.000 description 1
- 102100026967 T cell receptor beta chain MC.7.G5 Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 102100024995 Tetraspanin-14 Human genes 0.000 description 1
- 102100040952 Tetraspanin-7 Human genes 0.000 description 1
- 102100032802 Tetraspanin-8 Human genes 0.000 description 1
- 108700031126 Tetraspanins Proteins 0.000 description 1
- 102000043977 Tetraspanins Human genes 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 102100023019 Vesicle transport through interaction with t-SNAREs homolog 1A Human genes 0.000 description 1
- 102100023018 Vesicle transport through interaction with t-SNAREs homolog 1B Human genes 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 1
- 210000003425 amniotic epithelial cell Anatomy 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000000158 apoptosis inhibitor Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 1
- 229960002594 arsenic trioxide Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 229940087430 biaxin Drugs 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 210000000069 breast epithelial cell Anatomy 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 238000011965 cell line development Methods 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 229940026692 decadron Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229940115080 doxil Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 229940000733 emcyt Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000003013 erythroid precursor cell Anatomy 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940084910 gliadel Drugs 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000002467 interleukin receptors Human genes 0.000 description 1
- 108010093036 interleukin receptors Proteins 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 229940065638 intron a Drugs 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 108010090909 laminin gamma 1 Proteins 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 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
- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 108091051828 miR-122 stem-loop Proteins 0.000 description 1
- 108091066112 miR-122-1 stem-loop Proteins 0.000 description 1
- 108091057488 miR-122-2 stem-loop Proteins 0.000 description 1
- 108091043184 miR-1246 stem-loop Proteins 0.000 description 1
- 108091091207 miR-127 stem-loop Proteins 0.000 description 1
- 108091082518 miR-1290 stem-loop Proteins 0.000 description 1
- 108091058688 miR-141 stem-loop Proteins 0.000 description 1
- 108091086416 miR-192 stem-loop Proteins 0.000 description 1
- 108091039097 miR-193b stem-loop Proteins 0.000 description 1
- 108091054189 miR-196a stem-loop Proteins 0.000 description 1
- 108091062444 miR-196a-1 stem-loop Proteins 0.000 description 1
- 108091092367 miR-196a-2 stem-loop Proteins 0.000 description 1
- 108091041889 miR-196a-3 stem-loop Proteins 0.000 description 1
- 108091068947 miR-196a-4 stem-loop Proteins 0.000 description 1
- 108091050874 miR-19a stem-loop Proteins 0.000 description 1
- 108091086850 miR-19a-1 stem-loop Proteins 0.000 description 1
- 108091088468 miR-19a-2 stem-loop Proteins 0.000 description 1
- 108091037787 miR-19b stem-loop Proteins 0.000 description 1
- 108091059199 miR-200a stem-loop Proteins 0.000 description 1
- 108091089775 miR-200b stem-loop Proteins 0.000 description 1
- 108091063796 miR-206 stem-loop Proteins 0.000 description 1
- 108091041631 miR-21-1 stem-loop Proteins 0.000 description 1
- 108091044442 miR-21-2 stem-loop Proteins 0.000 description 1
- 108091048308 miR-210 stem-loop Proteins 0.000 description 1
- 108091061917 miR-221 stem-loop Proteins 0.000 description 1
- 108091063489 miR-221-1 stem-loop Proteins 0.000 description 1
- 108091055391 miR-221-2 stem-loop Proteins 0.000 description 1
- 108091031076 miR-221-3 stem-loop Proteins 0.000 description 1
- 108091092722 miR-23b stem-loop Proteins 0.000 description 1
- 108091031298 miR-23b-1 stem-loop Proteins 0.000 description 1
- 108091082339 miR-23b-2 stem-loop Proteins 0.000 description 1
- 108091065159 miR-339 stem-loop Proteins 0.000 description 1
- 108091023791 miR-339-1 stem-loop Proteins 0.000 description 1
- 108091079013 miR-34b Proteins 0.000 description 1
- 108091084018 miR-34b stem-loop Proteins 0.000 description 1
- 108091063470 miR-34b-1 stem-loop Proteins 0.000 description 1
- 108091049916 miR-34b-2 stem-loop Proteins 0.000 description 1
- 108091057222 miR-34b-3 stem-loop Proteins 0.000 description 1
- 108091092639 miR-34b-4 stem-loop Proteins 0.000 description 1
- 108091090583 miR-34c stem-loop Proteins 0.000 description 1
- 108091082133 miR-34c-1 stem-loop Proteins 0.000 description 1
- 108091028761 miR-409 stem-loop Proteins 0.000 description 1
- 108091092564 miR-494 stem-loop Proteins 0.000 description 1
- 108091063340 miR-497 stem-loop Proteins 0.000 description 1
- 108091047084 miR-9 stem-loop Proteins 0.000 description 1
- 108091076732 miR-99a stem-loop Proteins 0.000 description 1
- 108091064318 miR-99a-1 stem-loop Proteins 0.000 description 1
- 108091086202 miR-99a-2 stem-loop Proteins 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000004479 myeloid suppressor cell Anatomy 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000026415 nucleotide binding proteins Human genes 0.000 description 1
- 108091014756 nucleotide binding proteins Proteins 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000009984 peri-natal effect Effects 0.000 description 1
- 201000002628 peritoneum cancer Diseases 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229940116176 remicade Drugs 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 230000035806 respiratory chain Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940061353 temodar Drugs 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000000515 tooth Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000013413 tumor xenograft mouse model Methods 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940099039 velcade Drugs 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229940053867 xeloda Drugs 0.000 description 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2833—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6901—Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/04—Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0684—Cells of the urinary tract or kidneys
- C12N5/0686—Kidney cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/812—Breast
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle
-
- 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
- C12N2510/00—Genetically modified cells
- C12N2510/02—Cells for production
-
- 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
- C12N2527/00—Culture process characterised by the use of mechanical forces, e.g. strain, vibration
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Urology & Nephrology (AREA)
- Toxicology (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Sustainable Development (AREA)
- Botany (AREA)
- Inorganic Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Oncology (AREA)
- Mechanical Engineering (AREA)
Description
ベクターの構築及び細胞株の樹立
抗HLA-G VHH/CD63融合タンパク質をコードする配列を合成し、分子クローニング技術によりpcDNA3.4プラスミド(Thermo Scientific)に直列に挿入して、抗HLA-G-CD63発現プラスミド(pcDNA3.4-αHLA-G-CD63)を作製した。インサートのDNA配列は、サンガーシーケンシング法によって検証した。安定した発現細胞株を樹立するために、293T細胞を、リポフェクタミン3000試薬(Thermo Scientific)を用いて、pcDNA3.4-αHLA-G-CD63でトランスフェクトした。トランスフェクション後、安定にトランスフェクションされた293T細胞をG418(800μg/mL、Invivogen)での培養により選択した。293T細胞は、抗HLA-G/CD63融合タンパク質を有するエキソソームをカーゴエキソソーム(CARExo)として産生することができた。
エキソソーム(ExoまたはCARExo)を得るために、培地を2000gで15分間遠心分離して、細胞デブリを除去し、0.22μmの濾紙で濾過した。次いで、上清を限外濾過(Amicon(登録商標)Ultra,30kDa、Merck Millipore,Billerica,MA,USA)により、5000gで8分間濃縮した。回収した上清をタンジェンシャルフロー濾過(MAP.03プラスTFFシステム、Lefo Science,Taipei,Taiwan)を使用して、分子量300kDaのメンブレンで順次濾過し、上記で詳述したリン酸緩衝液(PBS)(pH=7.4)によって再懸濁した。すべてのサンプルは、即時使用に4℃で操作したが、さらに使用するために-80℃で保存した。単離後、Exo/CARExoを1%グルタルアルデヒドで、4℃で一晩固定した。洗浄後、Exo/CARExoをホルムバーカーボンコーティンググリッドに添加し、リンタングステン酸水溶液で1分間陰性染色した。Exo/CARExoの超微細構造を透過型電子顕微鏡(TEM,JEOL JEM-1400,Tokyo,Japan)によって解析した。
PKH26標識Exo/CARExoを2mL MDA-MB-231及びMCF10A培地(109Exo/mL)で混合した。最初に、これら2つの細胞株をμスライドウェル(ibidi GmbH,Grafelfing,Germany)で60%コンフルエントまで成長させて、次いで培地を、PKH26標識Exoを含む培地と交換した。6時間、12時間、及び24時間培養後、細胞をPBSで2回洗浄し、固定し、Alexa Fluor(商標)488ファロイジン及びDAPIで染色した。洗浄後、細胞の画像を蛍光顕微鏡(BX53,Olympus,Tokyo,Japan)を用いて撮影した。
細胞は、異なる時点で回収するために、Exo/CARExoを含む96ウェルで培養し、培養培地を回収し、PBS溶液で洗浄してあらゆる残留培地を除去した。テトラゾリウム色素MTT(3-(4,5-ジメチルチアゾール-2-イル)-2,5-ジフェニルテトラゾリウムブロミド)(Sigma-Aldrich)を1:9の比率で新鮮培地に混合し、呼吸鎖に作用することによって機能する細胞生存率を評価するために行った。3時間の反応後、MTT剤を除去し、DMSOを加えて20分間放置し、ホルマザン結晶を溶解し、96ウェルに均等に再分配した。吸光度は、細胞生存率を評価するために波長570nmで測定することによって定量した。
MDA-MB-231、MCF-7及びMCF-10A細胞(密度5x104細胞/mL)をカバースリップ付き35mmディッシュに播種し、12時間接着させた。MDA-MB-231、MCF-7及びMCF-10A細胞を、いずれかのナノプローブ(0μM及び5μM)の存在下で、37℃で6時間培養した。細胞をPBS中で1回洗浄し、固定し、1%Triton X-100を含むPBSと共に4%パラホルムアルデヒドを用いて同時に透過処理した。次に、0.1Mグリシンを含むPBSでクエンチし、3%(wt/vol)BSAで、4℃で一晩ブロッキングした。固定し、透過処理した細胞を、指示のとおり、一次抗体及び二次抗体で染色した。次いで、細胞を、室温で5分間、DAPI溶液により染色した。ヤギ抗マウスIgG h&L(Alexa Fluor(登録商標)647)(ab150115)及びヤギ抗ウサギIgG h&LAlexa Fluor(登録商標)488)(ab150077)をAbcam(Cambridge,UK)から入手した。細胞形態は、レーザー共焦点顕微鏡(Zessis,LSM800,Germany)を用いて観察した。
Exo/CARExoに外因性カーゴを取り込むために、miR-34a及びドキソルビシンをエレクトロポレーションによってトランスフェクトした。Exo/CARExoの量は、1x109(NTAで測定)であり、エレクトロポレーション前にmiR-34aを含むバッファーと混合した。エレクトロポレーション後、Exo/CARExoを37℃で1時間静置した。その後、ドキソルビシン1mgと混合し、37℃で60分間反応させた後、4℃に切り替えて30分間反応させ、その後、20μLのExoQuick-TC(System Bioscience)を加えて十分に混合し、4℃で16時間反応させた。反応後、1500xg、4℃で30分間遠心分離し、上清を吸引除去し、200μL PBSを加えて洗浄し、遠心分離により除去し、上記のPBS洗浄を2回繰り返し、最後に100μL PBSを加えてエキソソームを均一に分散させた。完了したときに、Exo/CARExoの数をNTAにより再分析し、薬物送達中に喪失したExo/CARExoの数を分析した。
本発明は、腫瘍異種移植マウスモデル(NOD/SCIDガンママウス)を用いて、in vivoでのExo/CARExoの腫瘍標的効果を評価した。PBS、Exo、及びCARExoは、100μL(5x1010Exo/CARExo)の尾静脈を介して注射させた。マウスは、異なる時点で走査し、24時間で屠殺した。
異種移植片腫瘍モデルは、0.1mLのMDA-MB-231細胞懸濁液(5x106/100μL)を右脇腹NOD/SCIDガンマ(NSG)ヌードマウスに注射することによって作製した。確立されたMDA-MB-231腫瘍(150~200mm3)担持マウスを無作為に群に分類し、その群を次のように処置した:(i)対照としてのPBS;(ii)Exo-miR;(iii)Exo-薬物;(iv)Exo-薬物-miR(薬物当量は、5mg/kg、miR当量は0.1nmoL/kg)。薬物は、7週間連続して尾静脈から毎週注射した。マウスの体重を測定し、腫瘍を4日毎にノギスにより測定した。腫瘍体積は、次式を用いて計算した:腫瘍体積=(長さx幅x幅)/2。
マウスは、1mL/kgの用量で、水和クロラール水溶液(3%w/v)の腹腔内注射を使用して麻酔した。その後、屠殺させ、血液のサンプルを採取し、腹腔を露出させた。肝臓、肺、脾臓、心臓及び腎臓のサンプルを回収し、ヘマトキシリン-エオジン染色の前に10%中性緩衝ホルマリン(NBF)に一時的に保存した。
すべての細胞をそれぞれの適切な培地で培養した。培養培地は、2日または3日ごとに交換した。脱細胞化肺ECM包埋培養の前に、本発明では、0.25%トリプシンを含むEDTA(Gibco)溶液で処理することによって、各細胞型を回収し、1200rpmで、10分間、遠心分離によって細胞を回収し、細胞を各培養培地に分散させた。細胞懸濁液を、様々な細胞について最終濃度5x106細胞ml-1となるようにECMのプレゲル溶液(4重量%)と混合した。各細胞封入プレゲル溶液のアリコートをマルチウェルプレートのウェルに移し、37℃のインキュベーターに1時間入れた。ゲル化後、がんまたは内皮細胞用の培養培地をウェルに添加した。各培養培地は、2日または3日ごとに交換した。
本発明では、鋳型成形プロセスを経て、成長刺激促進構造を有するヒドロゲルを作製した。成長刺激促進構造を有する細胞含有ヒドロゲルは引張バイオリアクターと適合性があるべきであることを考慮して、構築物を製造するために3つの成分、すなわちPluronic F-127溶液、GelMa、及び細胞含有FGelMaを使用した。押込み金型は、BioXバイオプリンタ(Cellink,Sweden)を使用して、Pluronic F-127(Sigma-Aldrich)溶液を蒸留水中30重量%の濃度で用いて、設計し、印刷した。図16A~図16Cは、成長刺激促進構築物の代表的な単位細胞を示す。金型印刷では、ステレオリソグラフィー(STL)モデルが、SolidWorksを使用して設計し、開発された。STLファイルは、gコードファイルに変換させ、sli3erソフトウェアを使用して、バイオプリンタの動き及び印刷経路を決定するために使用した。内径150μmのルアーロックノズルを備えたシリンジバレルに変色性(fugitive)インクを収容後、移動速度25mm/sのシリンジを用いて、空気圧170kPaを加えてスライドガラス上に変色性インクを堆積させ、直径約250μmを有するフィラメントを形成した。成長刺激促進構築物の変色性型は、構築物の最終厚が2.1mmに達するまで、層ごと(1層あたり150μm)に作製した。次に、15重量%のGelMa及び0.5重量%のI-2959を含む加温した(37℃)PBSを上記型に入れ、引張バイオリアクターに接続可能な、両側に2つの開口部を有する固定部を形成した(ATMS Boxer QQA Cyclic Stretch Culture System,Genemessenger,Kaohsiung,Taiwan)(図16A)。細胞含有FGelMaは、HEK293T(または他の正常細胞株及び初代細胞)を、10重量%FGelMaを含む0.5%I-2959含有PBSと混合することによって得た。培養培地で培養したコンフルエントな細胞をトリプシン処理し、遠心分離し、密度5x106細胞/mLで加温したFGelMa溶液に再懸濁した。次いで、細胞含有ヒドロゲルを試料の成長刺激促進部分に取り込んだ。試料を37℃で1分間インキュベートして、GelMa及びFGelMaを液体化した。UV照射(365nm)に90秒間曝露後、試料を冷(4℃)PBSに10分間浸漬し、変色性F-127を溶解した(図16B)。周期的引張力を加えるために、試料を引張バイオリアクターに固定し、培養培地8mLを加えた。培養期間中、細胞含有ヒドロゲルに20%の引張ひずみを0.48Hzの周波数で連続的に加えた。静置条件下で培養した試料を対照群とした(図16C)。すべてのin vitro実験は、37℃で5%CO2及び100%湿度の細胞培養インキュベーターで実施し、培地は、2日ごとに新鮮なものにした。
以前の結果において、本発明は、HEK293Tの引張刺激の存在は、細胞挙動において重要な役割を有する機械感受性転写活性化因子であるYAPタンパク質の細胞活性化を介するものであると考えられた。したがって、最終的に、本発明は、HEK293T含有成長刺激促進足場をYAP阻害剤であるベルテポルフィン(MedChemExpress,Monmouth Junction,NJ,USA)に曝露した。特定の日培養後、本発明では、免疫蛍光染色及び骨形成関連タンパク質を使用して、引張刺激におけるYAPの役割を評価した。
カーゴ工学技術を有するもの、有さないものの、エキソソームの特徴を検証した。形態学的結果は、タンジェンシャルフロー濾過(TFF)技術からのExo及びCARExoの単離のTEM画像で確認した。結果は、カーゴ工学技術によるものであっても、同様のレベルのエキソソームサイズを示した(図1A)。それらは、小胞中空特徴及び表面膜を明確に示した。NTA分析では、直径のメインピークが110nm(Exo)及び120nm(CARExo)に別々にあることが示された(図1B)。これらの結果により、カーゴ工学技術による処置後も、エキソソームの形態が安定していることが判明した。
Claims (10)
- 融合タンパク質を含むエキソソームを含む組成物であって、前記融合タンパク質が、標的タンパク質及びエキソソーム膜貫通タンパク質を含み、前記標的タンパク質が、抗HLA-Gタンパク質を含み、前記抗HLA-Gタンパク質の配列が、配列番号2を含む、組成物。
- 前記エキソソーム膜貫通タンパク質が、CD9、CD63またはCD81を含む、請求項1に記載の組成物。
- 前記エキソソームが、抗がん剤を含む、請求項1に記載の組成物。
- 前記抗がん剤が、がんを治療するための化学療法剤またはマイクロRNAを含む、請求項3に記載の組成物。
- がんを治療するための薬物を調製するための組成物の使用であって、前記組成物が、治療用エキソソームを含み、前記治療用エキソソームが、融合タンパク質及び抗がん剤を含み、前記融合タンパク質が、標的タンパク質及びエキソソーム膜貫通タンパク質を含み、前記標的タンパク質が、抗HLA-Gタンパク質を含み、前記抗HLA-Gタンパク質の配列が、配列番号2を含む、使用。
- 前記エキソソーム膜貫通タンパク質が、CD9、CD63またはCD81を含む、請求項5に記載の使用。
- 前記がんが、乳癌、肺癌、口腔癌、肝癌、大腸癌、膠芽腫、髄芽腫、膀胱癌、膵癌、または卵巣癌を含む、請求項5に記載の使用。
- 前記抗がん剤が、がんを治療するための化学療法剤またはマイクロRNAを含む、請求項5に記載の使用。
- 前記化学療法剤が、ドキソルビシン、タキソテール、シスプラチン、ハーセプチン、パージェタ、エピルビシン、シクロホスファミド、カルボプラチン、ゲムシタビン、またはペメトレキセド、またはこれらの組み合わせを含む、請求項8に記載の使用。
- がんを治療するためのマイクロRNAが、miR-34aを含む請求項8に記載の使用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2024075581A JP2024105433A (ja) | 2021-12-03 | 2024-05-08 | エキソソームの産生及びその使用 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202163285493P | 2021-12-03 | 2021-12-03 | |
US63/285,493 | 2021-12-03 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024075581A Division JP2024105433A (ja) | 2021-12-03 | 2024-05-08 | エキソソームの産生及びその使用 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2023083256A JP2023083256A (ja) | 2023-06-15 |
JP7510634B2 true JP7510634B2 (ja) | 2024-07-04 |
Family
ID=84387578
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022193265A Active JP7510634B2 (ja) | 2021-12-03 | 2022-12-02 | エキソソームの産生及びその使用 |
JP2024075581A Pending JP2024105433A (ja) | 2021-12-03 | 2024-05-08 | エキソソームの産生及びその使用 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2024075581A Pending JP2024105433A (ja) | 2021-12-03 | 2024-05-08 | エキソソームの産生及びその使用 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20230211009A1 (ja) |
EP (1) | EP4190349A3 (ja) |
JP (2) | JP7510634B2 (ja) |
CN (1) | CN116218780A (ja) |
TW (2) | TW202415768A (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117511870B (zh) * | 2024-01-03 | 2024-04-19 | 广东先康达生物科技有限公司 | 具有免疫调控的复合细胞外泌体制剂的制备方法及其应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019523407A (ja) | 2016-07-21 | 2019-08-22 | エヴォックス・セラピューティクス・リミテッド | Fc結合能を有する融合タンパク質を含む細胞外小胞の使用 |
JP2020043848A (ja) | 2018-09-17 | 2020-03-26 | 中國醫藥大學附設醫院China Medical University Hospital | キメラ抗原受容体、核酸、キメラ抗原受容体発現プラスミド、キメラ抗原受容体発現細胞、その使用及びがん治療用の医薬組成物 |
WO2020257710A1 (en) | 2019-06-21 | 2020-12-24 | Entelexo Biotherapeutics Inc. | Platforms, compositions, and methods for therapeutics delivery |
JP2021065219A (ja) | 2019-10-24 | 2021-04-30 | 中國醫藥大學附設醫院China Medical University Hospital | Hla−g特異的キメラ抗原受容体、核酸、hla−g特異的キメラ抗原受容体発現プラスミド、hla−g特異的キメラ抗原受容体発現細胞及び癌治療用の医薬組成物 |
WO2021211633A2 (en) | 2020-04-13 | 2021-10-21 | Mantra Bio, Inc. | Modular binding proteins for extracellular vesicles and uses thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US12012454B2 (en) * | 2021-03-24 | 2024-06-18 | China Medical University Hospital | Anti-tumor antigen nanobody and nucleic acid encoding sequence thereof, and uses of the same |
US11795227B2 (en) * | 2021-03-24 | 2023-10-24 | Shine-On Biomedical Co., Ltd. | Immunomodulation and anti-tumor-related nanobody and nucleic acid encoding sequence thereof, and uses of the same |
-
2022
- 2022-12-02 JP JP2022193265A patent/JP7510634B2/ja active Active
- 2022-12-02 TW TW112147849A patent/TW202415768A/zh unknown
- 2022-12-02 EP EP22211115.5A patent/EP4190349A3/en active Pending
- 2022-12-02 CN CN202211541803.9A patent/CN116218780A/zh active Pending
- 2022-12-02 US US18/060,966 patent/US20230211009A1/en active Pending
- 2022-12-02 TW TW111146383A patent/TWI836766B/zh active
-
2024
- 2024-05-08 JP JP2024075581A patent/JP2024105433A/ja active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019523407A (ja) | 2016-07-21 | 2019-08-22 | エヴォックス・セラピューティクス・リミテッド | Fc結合能を有する融合タンパク質を含む細胞外小胞の使用 |
JP2020043848A (ja) | 2018-09-17 | 2020-03-26 | 中國醫藥大學附設醫院China Medical University Hospital | キメラ抗原受容体、核酸、キメラ抗原受容体発現プラスミド、キメラ抗原受容体発現細胞、その使用及びがん治療用の医薬組成物 |
WO2020257710A1 (en) | 2019-06-21 | 2020-12-24 | Entelexo Biotherapeutics Inc. | Platforms, compositions, and methods for therapeutics delivery |
JP2021065219A (ja) | 2019-10-24 | 2021-04-30 | 中國醫藥大學附設醫院China Medical University Hospital | Hla−g特異的キメラ抗原受容体、核酸、hla−g特異的キメラ抗原受容体発現プラスミド、hla−g特異的キメラ抗原受容体発現細胞及び癌治療用の医薬組成物 |
WO2021211633A2 (en) | 2020-04-13 | 2021-10-21 | Mantra Bio, Inc. | Modular binding proteins for extracellular vesicles and uses thereof |
Non-Patent Citations (1)
Title |
---|
Chimeric Antigen Receptor-Engineered Exosome As a Drug Delivery System in Mantle Cell Lymphoma,Blood,2017年,Vol.130 suppl.1,p.5561 |
Also Published As
Publication number | Publication date |
---|---|
CN116218780A (zh) | 2023-06-06 |
TW202325319A (zh) | 2023-07-01 |
JP2024105433A (ja) | 2024-08-06 |
EP4190349A2 (en) | 2023-06-07 |
TW202415768A (zh) | 2024-04-16 |
TWI836766B (zh) | 2024-03-21 |
EP4190349A3 (en) | 2023-08-30 |
US20230211009A1 (en) | 2023-07-06 |
JP2023083256A (ja) | 2023-06-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP3706796B1 (en) | Exosomes comprising rna therapeutics | |
Fu et al. | Recent progress in microRNA-based delivery systems for the treatment of human disease | |
Feng et al. | Folic acid-modified Exosome-PH20 enhances the efficiency of therapy via modulation of the tumor microenvironment and directly inhibits tumor cell metastasis | |
Schulz-Siegmund et al. | Nucleic acid delivery with extracellular vesicles | |
US20200316226A1 (en) | Engineered extracellular vesicles for enhanced tissue delivery | |
JP6137894B2 (ja) | リポソーム−エキソソームハイブリッドベシクル及びその調製法 | |
CN109893660B (zh) | 一种用于脑胶质瘤治疗的仿生纳米载体及其制备方法 | |
US20210238248A1 (en) | Engineering Extracellular Vesicles for Affinity Purification | |
JP2024105433A (ja) | エキソソームの産生及びその使用 | |
WO2019043709A1 (en) | COMPOSITIONS AND METHODS FOR TREATING FIBROTIC DISEASES | |
KR102461933B1 (ko) | 연골조직 재건 또는 재생을 위한 유전자 전달체 및 이를 이용한 연골세포로의 분화방법 | |
Ren et al. | A targeting delivery system for effective genome editing in leukemia cells to reverse malignancy | |
KR20240138577A (ko) | 엑소좀의 생산 및 이의 용도 | |
Dilsiz | Exosomes as new generation vehicles for drug delivery systems | |
AU2023201146A1 (en) | Production of exosomes and uses thereof | |
Asad et al. | Current non-viral gene therapy strategies for the treatment of glioblastoma | |
US20240238418A1 (en) | Car t cell therapy method | |
Ghaemi et al. | Robust aptamer-targeted CRISPR/Cas9 delivery using mesenchymal stem cell membrane–liposome hybrid: BIRC5 gene knockout against melanoma | |
Paul et al. | ExoDS: a versatile exosome-based drug delivery platform to target cancer cells and cancer stem cells | |
CN115873905A (zh) | 一种gd2纳米抗体靶向修饰的类外泌体的新型药物载体的制备方法 | |
WO2023196232A1 (en) | Method of characterizing tumors | |
KR20230047126A (ko) | 선택적 폐 전달을 위한 폴리(아민-코-에스테르) 중합체성 입자 | |
Wang | Design of multifunctional nanomaterials to improve cancer gene therapy | |
Way | Folate receptor-targeting liposomes for the delivery of antisense molecules to cancer cells | |
Brunetto | Investigation of Cancer Stem Cells (CSCs)-derived exosomes and their influence on the tumor microenvironment |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20230203 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20240125 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240305 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240508 |
|
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: 20240528 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240613 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7510634 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |