JP2018516249A - フェロトーシスを介して栄養欠乏がん細胞の細胞死を誘導するための極小ナノ粒子を使用する処置方法 - Google Patents
フェロトーシスを介して栄養欠乏がん細胞の細胞死を誘導するための極小ナノ粒子を使用する処置方法 Download PDFInfo
- Publication number
- JP2018516249A JP2018516249A JP2017560717A JP2017560717A JP2018516249A JP 2018516249 A JP2018516249 A JP 2018516249A JP 2017560717 A JP2017560717 A JP 2017560717A JP 2017560717 A JP2017560717 A JP 2017560717A JP 2018516249 A JP2018516249 A JP 2018516249A
- Authority
- JP
- Japan
- Prior art keywords
- nanoparticles
- tumor tissue
- dots
- ferrotosis
- high concentration
- 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.)
- Granted
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 311
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 258
- 230000030833 cell death Effects 0.000 title claims abstract description 137
- 238000011282 treatment Methods 0.000 title claims abstract description 115
- 238000000034 method Methods 0.000 title claims abstract description 104
- 230000002950 deficient Effects 0.000 title claims description 58
- 201000011510 cancer Diseases 0.000 title claims description 42
- 230000001939 inductive effect Effects 0.000 title claims description 16
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 102
- 229910052742 iron Inorganic materials 0.000 claims abstract description 51
- 238000009825 accumulation Methods 0.000 claims abstract description 41
- 239000003642 reactive oxygen metabolite Substances 0.000 claims abstract description 25
- 230000001419 dependent effect Effects 0.000 claims abstract description 19
- 230000017074 necrotic cell death Effects 0.000 claims abstract description 19
- 210000004027 cell Anatomy 0.000 claims description 249
- 210000001519 tissue Anatomy 0.000 claims description 159
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 97
- 150000001413 amino acids Chemical class 0.000 claims description 95
- 239000000203 mixture Substances 0.000 claims description 55
- 239000000377 silicon dioxide Substances 0.000 claims description 47
- 239000003814 drug Substances 0.000 claims description 45
- WHNFPRLDDSXQCL-UAZQEYIDSA-N α-msh Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H](CO)NC(C)=O)C1=CC=C(O)C=C1 WHNFPRLDDSXQCL-UAZQEYIDSA-N 0.000 claims description 44
- 229940079593 drug Drugs 0.000 claims description 38
- 230000006698 induction Effects 0.000 claims description 37
- 230000008685 targeting Effects 0.000 claims description 28
- 229940127089 cytotoxic agent Drugs 0.000 claims description 23
- 239000002246 antineoplastic agent Substances 0.000 claims description 22
- 229920001223 polyethylene glycol Polymers 0.000 claims description 20
- 201000001441 melanoma Diseases 0.000 claims description 17
- 102400000740 Melanocyte-stimulating hormone alpha Human genes 0.000 claims description 14
- 101710200814 Melanotropin alpha Proteins 0.000 claims description 14
- 230000001225 therapeutic effect Effects 0.000 claims description 14
- 230000004806 ferroptosis Effects 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 12
- 229940088597 hormone Drugs 0.000 claims description 11
- 239000005556 hormone Substances 0.000 claims description 11
- 101800001751 Melanocyte-stimulating hormone alpha Proteins 0.000 claims description 10
- 208000020816 lung neoplasm Diseases 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 8
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 8
- 238000011284 combination treatment Methods 0.000 claims description 8
- 210000003734 kidney Anatomy 0.000 claims description 8
- 201000002528 pancreatic cancer Diseases 0.000 claims description 8
- 210000004881 tumor cell Anatomy 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 238000012377 drug delivery Methods 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 102100027467 Pro-opiomelanocortin Human genes 0.000 claims description 6
- 230000002519 immonomodulatory effect Effects 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 125000005647 linker group Chemical group 0.000 claims description 5
- 210000000496 pancreas Anatomy 0.000 claims description 5
- 230000029663 wound healing Effects 0.000 claims description 5
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 210000004556 brain Anatomy 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 230000017423 tissue regeneration Effects 0.000 claims description 4
- 208000037841 lung tumor Diseases 0.000 claims description 3
- 229920000620 organic polymer Polymers 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- 230000007246 mechanism Effects 0.000 abstract description 22
- 235000015097 nutrients Nutrition 0.000 abstract description 14
- 230000001413 cellular effect Effects 0.000 abstract description 6
- 230000001360 synchronised effect Effects 0.000 abstract description 4
- 230000037353 metabolic pathway Effects 0.000 abstract description 3
- 239000002245 particle Substances 0.000 description 125
- 235000001014 amino acid Nutrition 0.000 description 87
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 82
- 238000002474 experimental method Methods 0.000 description 54
- 229960003180 glutathione Drugs 0.000 description 40
- 239000002609 medium Substances 0.000 description 38
- 108010024636 Glutathione Proteins 0.000 description 36
- 241000699670 Mus sp. Species 0.000 description 32
- 210000002540 macrophage Anatomy 0.000 description 29
- 238000011002 quantification Methods 0.000 description 25
- 230000006907 apoptotic process Effects 0.000 description 24
- 230000000694 effects Effects 0.000 description 23
- 230000004614 tumor growth Effects 0.000 description 23
- 108090000765 processed proteins & peptides Proteins 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 230000021597 necroptosis Effects 0.000 description 17
- 230000004044 response Effects 0.000 description 17
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 16
- 230000034994 death Effects 0.000 description 16
- 239000000463 material Substances 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 15
- 102000016942 Elastin Human genes 0.000 description 14
- 108010014258 Elastin Proteins 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- 229920002549 elastin Polymers 0.000 description 14
- 230000004900 autophagic degradation Effects 0.000 description 13
- 235000003642 hunger Nutrition 0.000 description 13
- 238000001727 in vivo Methods 0.000 description 13
- 238000005259 measurement Methods 0.000 description 13
- 230000037351 starvation Effects 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 230000002132 lysosomal effect Effects 0.000 description 12
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 11
- DJZCTUVALDDONK-HQMSUKCRSA-N concanamycin A Chemical compound O1C(=O)\C(OC)=C\C(\C)=C\[C@@H](C)[C@@H](O)[C@@H](CC)[C@@H](O)[C@H](C)C\C(C)=C\C=C\[C@H](OC)[C@H]1[C@@H](C)[C@@H](O)[C@H](C)[C@]1(O)O[C@H](\C=C\C)[C@@H](C)[C@H](O[C@@H]2O[C@H](C)[C@@H](OC(N)=O)[C@H](O)C2)C1 DJZCTUVALDDONK-HQMSUKCRSA-N 0.000 description 11
- DJZCTUVALDDONK-UHFFFAOYSA-N concanamycin A Natural products O1C(=O)C(OC)=CC(C)=CC(C)C(O)C(CC)C(O)C(C)CC(C)=CC=CC(OC)C1C(C)C(O)C(C)C1(O)OC(C=CC)C(C)C(OC2OC(C)C(OC(N)=O)C(O)C2)C1 DJZCTUVALDDONK-UHFFFAOYSA-N 0.000 description 11
- 229960000958 deferoxamine Drugs 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 210000003712 lysosome Anatomy 0.000 description 11
- 230000001868 lysosomic effect Effects 0.000 description 11
- 230000002285 radioactive effect Effects 0.000 description 11
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 229960004308 acetylcysteine Drugs 0.000 description 10
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 150000002632 lipids Chemical class 0.000 description 10
- 238000011068 loading method Methods 0.000 description 10
- 239000000523 sample Substances 0.000 description 10
- 108010033024 Phospholipid Hydroperoxide Glutathione Peroxidase Proteins 0.000 description 9
- 102100023410 Phospholipid hydroperoxide glutathione peroxidase Human genes 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 238000010186 staining Methods 0.000 description 9
- 230000004913 activation Effects 0.000 description 8
- 235000010323 ascorbic acid Nutrition 0.000 description 8
- 229960005070 ascorbic acid Drugs 0.000 description 8
- 239000011668 ascorbic acid Substances 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 8
- 230000036961 partial effect Effects 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- KJQFBVYMGADDTQ-CVSPRKDYSA-N L-buthionine-(S,R)-sulfoximine Chemical compound CCCCS(=N)(=O)CC[C@H](N)C(O)=O KJQFBVYMGADDTQ-CVSPRKDYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 238000006731 degradation reaction Methods 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 239000000975 dye Substances 0.000 description 7
- UJHBVMHOBZBWMX-UHFFFAOYSA-N ferrostatin-1 Chemical compound NC1=CC(C(=O)OCC)=CC=C1NC1CCCCC1 UJHBVMHOBZBWMX-UHFFFAOYSA-N 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 229920000642 polymer Polymers 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 238000002287 time-lapse microscopy Methods 0.000 description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 6
- 102100034216 Melanocyte-stimulating hormone receptor Human genes 0.000 description 6
- 108010021428 Type 1 Melanocortin Receptor Proteins 0.000 description 6
- 208000009956 adenocarcinoma Diseases 0.000 description 6
- FRHBOQMZUOWXQL-UHFFFAOYSA-L ammonium ferric citrate Chemical compound [NH4+].[Fe+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FRHBOQMZUOWXQL-UHFFFAOYSA-L 0.000 description 6
- 102000055102 bcl-2-Associated X Human genes 0.000 description 6
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000007850 fluorescent dye Substances 0.000 description 6
- 230000009036 growth inhibition Effects 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 239000004313 iron ammonium citrate Substances 0.000 description 6
- 235000000011 iron ammonium citrate Nutrition 0.000 description 6
- 201000005202 lung cancer Diseases 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 238000002600 positron emission tomography Methods 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- 102000000546 Apoferritins Human genes 0.000 description 5
- 108010002084 Apoferritins Proteins 0.000 description 5
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 5
- 101150017888 Bcl2 gene Proteins 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 206010033128 Ovarian cancer Diseases 0.000 description 5
- 206010038389 Renal cancer Diseases 0.000 description 5
- 206010042971 T-cell lymphoma Diseases 0.000 description 5
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 5
- 210000003690 classically activated macrophage Anatomy 0.000 description 5
- 238000002648 combination therapy Methods 0.000 description 5
- 239000010949 copper Substances 0.000 description 5
- 229960004642 ferric ammonium citrate Drugs 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 238000003384 imaging method Methods 0.000 description 5
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000002503 metabolic effect Effects 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 208000008443 pancreatic carcinoma Diseases 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
- 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 description 4
- 208000017604 Hodgkin disease Diseases 0.000 description 4
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 4
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 4
- 229930182555 Penicillin Natural products 0.000 description 4
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
- 206010039491 Sarcoma Diseases 0.000 description 4
- 238000001772 Wald test Methods 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000000562 conjugate Substances 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 230000002354 daily effect Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 229960004679 doxorubicin Drugs 0.000 description 4
- 239000010931 gold Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000011532 immunohistochemical staining Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 201000010982 kidney cancer Diseases 0.000 description 4
- 230000003859 lipid peroxidation Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- -1 maytansinoid Chemical compound 0.000 description 4
- 229910052752 metalloid Inorganic materials 0.000 description 4
- 150000002738 metalloids Chemical class 0.000 description 4
- 150000002739 metals Chemical class 0.000 description 4
- 229910052755 nonmetal Inorganic materials 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 4
- 229920001610 polycaprolactone Polymers 0.000 description 4
- 230000000770 proinflammatory effect Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- BXTJCSYMGFJEID-XMTADJHZSA-N (2s)-2-[[(2r,3r)-3-[(2s)-1-[(3r,4s,5s)-4-[[(2s)-2-[[(2s)-2-[6-[3-[(2r)-2-amino-2-carboxyethyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]hexanoyl-methylamino]-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-met Chemical compound C([C@H](NC(=O)[C@H](C)[C@@H](OC)[C@@H]1CCCN1C(=O)C[C@H]([C@H]([C@@H](C)CC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN1C(C(SC[C@H](N)C(O)=O)CC1=O)=O)C(C)C)OC)C(O)=O)C1=CC=CC=C1 BXTJCSYMGFJEID-XMTADJHZSA-N 0.000 description 3
- TXUWMXQFNYDOEZ-UHFFFAOYSA-N 5-(1H-indol-3-ylmethyl)-3-methyl-2-sulfanylidene-4-imidazolidinone Chemical compound O=C1N(C)C(=S)NC1CC1=CNC2=CC=CC=C12 TXUWMXQFNYDOEZ-UHFFFAOYSA-N 0.000 description 3
- 102000007469 Actins Human genes 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 206010018338 Glioma Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 208000009905 Neurofibromatoses Diseases 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 229940049595 antibody-drug conjugate Drugs 0.000 description 3
- 101150096483 atg5 gene Proteins 0.000 description 3
- 230000004642 autophagic pathway Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004820 blood count Methods 0.000 description 3
- 238000010822 cell death assay Methods 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 230000005754 cellular signaling Effects 0.000 description 3
- 208000006990 cholangiocarcinoma Diseases 0.000 description 3
- 230000008045 co-localization Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 229920006237 degradable polymer Polymers 0.000 description 3
- 230000000779 depleting effect Effects 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 238000000799 fluorescence microscopy Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 208000014829 head and neck neoplasm Diseases 0.000 description 3
- 208000025750 heavy chain disease Diseases 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000012216 imaging agent Substances 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000010189 intracellular transport Effects 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 3
- 201000004931 neurofibromatosis Diseases 0.000 description 3
- 235000018343 nutrient deficiency Nutrition 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920000747 poly(lactic acid) Polymers 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 3
- 230000007306 turnover Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- 201000003076 Angiosarcoma Diseases 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 description 2
- 206010005949 Bone cancer Diseases 0.000 description 2
- 208000018084 Bone neoplasm Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 201000004085 CLL/SLL Diseases 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 108010062580 Concanavalin A Proteins 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 102000008857 Ferritin Human genes 0.000 description 2
- 108050000784 Ferritin Proteins 0.000 description 2
- 238000008416 Ferritin Methods 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 108010063907 Glutathione Reductase Proteins 0.000 description 2
- 102100036442 Glutathione reductase, mitochondrial Human genes 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
- 208000001258 Hemangiosarcoma Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001089266 Homo sapiens Receptor-interacting serine/threonine-protein kinase 3 Proteins 0.000 description 2
- 206010070999 Intraductal papillary mucinous neoplasm Diseases 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- 208000018142 Leiomyosarcoma Diseases 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 208000002720 Malnutrition Diseases 0.000 description 2
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 2
- 229930126263 Maytansine Natural products 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 208000014767 Myeloproliferative disease Diseases 0.000 description 2
- 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 description 2
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 2
- 208000033755 Neutrophilic Chronic Leukemia Diseases 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 2
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 229920002732 Polyanhydride Polymers 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 102100033729 Receptor-interacting serine/threonine-protein kinase 3 Human genes 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 102000008233 Toll-Like Receptor 4 Human genes 0.000 description 2
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 102000011731 Vacuolar Proton-Translocating ATPases Human genes 0.000 description 2
- 108010037026 Vacuolar Proton-Translocating ATPases Proteins 0.000 description 2
- 208000008383 Wilms tumor Diseases 0.000 description 2
- MIFGOLAMNLSLGH-QOKNQOGYSA-N Z-Val-Ala-Asp(OMe)-CH2F Chemical compound COC(=O)C[C@@H](C(=O)CF)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)OCC1=CC=CC=C1 MIFGOLAMNLSLGH-QOKNQOGYSA-N 0.000 description 2
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 208000017733 acquired polycythemia vera Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000000611 antibody drug conjugate Substances 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 210000004957 autophagosome Anatomy 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
- 208000002458 carcinoid tumor Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 208000023738 chronic lymphocytic leukemia/small lymphocytic lymphoma Diseases 0.000 description 2
- 201000010903 chronic neutrophilic leukemia Diseases 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000021615 conjugation Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 229940109262 curcumin Drugs 0.000 description 2
- 239000004148 curcumin Substances 0.000 description 2
- 235000012754 curcumin Nutrition 0.000 description 2
- 239000002254 cytotoxic agent Substances 0.000 description 2
- 231100000599 cytotoxic agent Toxicity 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229930013356 epothilone Natural products 0.000 description 2
- 201000004101 esophageal cancer Diseases 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
- 238000011156 evaluation Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 238000002060 fluorescence correlation spectroscopy Methods 0.000 description 2
- 229940014144 folate Drugs 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 201000009277 hairy cell leukemia Diseases 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 2
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 208000012804 lymphangiosarcoma Diseases 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 2
- 229960005558 mertansine Drugs 0.000 description 2
- ANZJBCHSOXCCRQ-FKUXLPTCSA-N mertansine Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCS)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 ANZJBCHSOXCCRQ-FKUXLPTCSA-N 0.000 description 2
- 150000001247 metal acetylides Chemical class 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 206010028537 myelofibrosis Diseases 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- 201000008026 nephroblastoma Diseases 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 238000012634 optical imaging Methods 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000012660 pharmacological inhibitor Substances 0.000 description 2
- 238000001637 plasma atomic emission spectroscopy Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920006210 poly(glycolide-co-caprolactone) Polymers 0.000 description 2
- 229920001306 poly(lactide-co-caprolactone) Polymers 0.000 description 2
- 229920002721 polycyanoacrylate Polymers 0.000 description 2
- 208000037244 polycythemia vera Diseases 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229920000570 polyether Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 208000003476 primary myelofibrosis Diseases 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 239000000700 radioactive tracer Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- WUILNKCFCLNXOK-CFBAGHHKSA-N salirasib Chemical group CC(C)=CCC\C(C)=C\CC\C(C)=C\CSC1=CC=CC=C1C(O)=O WUILNKCFCLNXOK-CFBAGHHKSA-N 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 201000002314 small intestine cancer Diseases 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 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
- 238000012360 testing method Methods 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 230000030968 tissue homeostasis Effects 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 230000037314 wound repair Effects 0.000 description 2
- MFZSNESUTRVBQX-XEURHVNRSA-N (2S)-2-amino-6-[4-[[3-[[(2S)-1-[[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]disulfanyl]pentanoylamino]hexanoic acid Chemical compound CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)[C@H](C)N(C)C(=O)CCSSC(C)CCC(=O)NCCCC[C@H](N)C(O)=O)[C@]2(C)O[C@H]2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2 MFZSNESUTRVBQX-XEURHVNRSA-N 0.000 description 1
- ORFNVPGICPYLJV-YTVPMEHESA-N (2s)-2-[[(2r,3r)-3-[(2s)-1-[(3r,4s,5s)-4-[[(2s)-2-[[(2s)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoyl-methylamino]-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl]amino]-3-phenylpropan Chemical compound C([C@H](NC(=O)[C@H](C)[C@@H](OC)[C@@H]1CCCN1C(=O)C[C@H]([C@H]([C@@H](C)CC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN1C(C=CC1=O)=O)C(C)C)OC)C(O)=O)C1=CC=CC=C1 ORFNVPGICPYLJV-YTVPMEHESA-N 0.000 description 1
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 1
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
- FBKFDSUZBVDZIX-FFGDOFBPSA-N (4s)-4-[[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-acetamido-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-2-methylpropanoyl]amino]-3-[4-(phosphonomethyl)phenyl]propanoyl]amino]-3-(6-chloro-1h-indol-3-yl)propanoyl]amino]-5-[[1-[[(2s)-1-amino-4-meth Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NC(C)(C)C(=O)N[C@@H](CC=1C=CC(CP(O)(O)=O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=C(Cl)C=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)NC1(CC1)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(C)=O)C1=CC=CC=C1 FBKFDSUZBVDZIX-FFGDOFBPSA-N 0.000 description 1
- VQVUBYASAICPFU-UHFFFAOYSA-N (6'-acetyloxy-2',7'-dichloro-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl) acetate Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(Cl)=C(OC(C)=O)C=C1OC1=C2C=C(Cl)C(OC(=O)C)=C1 VQVUBYASAICPFU-UHFFFAOYSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- ZOHXWSHGANNQGO-DSIKUUPMSA-N 1-amino-4-[[5-[[(2S)-1-[[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-2-methyl-5-oxopentan-2-yl]disulfanyl]-1-oxobutane-2-sulfonic acid Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCC(C)(C)SSCCC(C(N)=O)S(O)(=O)=O)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 ZOHXWSHGANNQGO-DSIKUUPMSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- DJQYYYCQOZMCRC-UHFFFAOYSA-N 2-aminopropane-1,3-dithiol Chemical compound SCC(N)CS DJQYYYCQOZMCRC-UHFFFAOYSA-N 0.000 description 1
- ODADKLYLWWCHNB-UHFFFAOYSA-N 2R-delta-tocotrienol Natural products OC1=CC(C)=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 ODADKLYLWWCHNB-UHFFFAOYSA-N 0.000 description 1
- OTXNTMVVOOBZCV-UHFFFAOYSA-N 2R-gamma-tocotrienol Natural products OC1=C(C)C(C)=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 OTXNTMVVOOBZCV-UHFFFAOYSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- 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 description 1
- JHSXDAWGLCZYSM-UHFFFAOYSA-N 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide Chemical compound CC1=CC(Cl)=CC=C1OCCCC(=O)NO JHSXDAWGLCZYSM-UHFFFAOYSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-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
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 description 1
- 208000036764 Adenocarcinoma of the esophagus Diseases 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 208000012791 Alpha-heavy chain disease Diseases 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 206010073360 Appendix cancer Diseases 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 101100034357 Arabidopsis thaliana RIPK gene Proteins 0.000 description 1
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 108010082399 Autophagy-Related Proteins Proteins 0.000 description 1
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
- 208000029862 Barrett adenocarcinoma Diseases 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006417 Bronchial carcinoma Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 241000283707 Capra Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010007275 Carcinoid tumour Diseases 0.000 description 1
- 102000003952 Caspase 3 Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 101710164760 Chlorotoxin Proteins 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 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
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- 108090000323 DNA Topoisomerases Proteins 0.000 description 1
- 102000003915 DNA Topoisomerases Human genes 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 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 description 1
- 241000283086 Equidae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010053717 Fibrous histiocytoma Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 229910005793 GeO 2 Inorganic materials 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010081687 Glutamate-cysteine ligase Proteins 0.000 description 1
- 102100033398 Glutamate-cysteine ligase regulatory subunit 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
- 206010018910 Haemolysis Diseases 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 206010020631 Hypergammaglobulinaemia benign monoclonal Diseases 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 208000007866 Immunoproliferative Small Intestinal Disease Diseases 0.000 description 1
- 201000003803 Inflammatory myofibroblastic tumor Diseases 0.000 description 1
- 206010067917 Inflammatory myofibroblastic tumour Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 101710157897 Interferon regulatory factor 5 Proteins 0.000 description 1
- 102100030131 Interferon regulatory factor 5 Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 206010061252 Intraocular melanoma Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 206010065973 Iron Overload Diseases 0.000 description 1
- 208000009164 Islet Cell Adenoma Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 1
- 239000002146 L01XE16 - Crizotinib Substances 0.000 description 1
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 108010009254 Lysosomal-Associated Membrane Protein 1 Proteins 0.000 description 1
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 1
- 210000004322 M2 macrophage Anatomy 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 208000032271 Malignant tumor of penis Diseases 0.000 description 1
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
- 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 1
- 102000046795 Mitogen-Activated Protein Kinase 3 Human genes 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 208000012799 Mu-heavy chain disease Diseases 0.000 description 1
- 208000002231 Muscle Neoplasms Diseases 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 206010028561 Myeloid metaplasia Diseases 0.000 description 1
- 102000003896 Myeloperoxidases Human genes 0.000 description 1
- 108090000235 Myeloperoxidases Proteins 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000009277 Neuroectodermal Tumors Diseases 0.000 description 1
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 1
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
- 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 108010016076 Octreotide Proteins 0.000 description 1
- 206010030137 Oesophageal adenocarcinoma Diseases 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 1
- 101150071716 PCSK1 gene Proteins 0.000 description 1
- 208000017459 Paget disease of the penis Diseases 0.000 description 1
- 208000025610 Paget disease of the vulva Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 206010034811 Pharyngeal cancer Diseases 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 102100040990 Platelet-derived growth factor subunit B Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920001273 Polyhydroxy acid Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 206010036524 Precursor B-lymphoblastic lymphomas Diseases 0.000 description 1
- 208000032758 Precursor T-lymphoblastic lymphoma/leukaemia Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010020147 Protein Corona Proteins 0.000 description 1
- 108010019674 Proto-Oncogene Proteins c-sis Proteins 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- KQXDHUJYNAXLNZ-XQSDOZFQSA-N Salinomycin Chemical compound O1[C@@H]([C@@H](CC)C(O)=O)CC[C@H](C)[C@@H]1[C@@H](C)[C@H](O)[C@H](C)C(=O)[C@H](CC)[C@@H]1[C@@H](C)C[C@@H](C)[C@@]2(C=C[C@@H](O)[C@@]3(O[C@@](C)(CC3)[C@@H]3O[C@@H](C)[C@@](O)(CC)CC3)O2)O1 KQXDHUJYNAXLNZ-XQSDOZFQSA-N 0.000 description 1
- 239000004189 Salinomycin Substances 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 201000008736 Systemic mastocytosis Diseases 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 239000006180 TBST buffer Substances 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 206010043515 Throat cancer Diseases 0.000 description 1
- 229910010413 TiO 2 Inorganic materials 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 206010046431 Urethral cancer Diseases 0.000 description 1
- 206010046458 Urethral neoplasms Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 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
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 241000021375 Xenogenes Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- IEDXPSOJFSVCKU-HOKPPMCLSA-N [4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[6-(2,5-dioxopyrrolidin-1-yl)hexanoylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methyl N-[(2S)-1-[[(2S)-1-[[(3R,4S,5S)-1-[(2S)-2-[(1R,2R)-3-[[(1S,2R)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-N-methylcarbamate Chemical compound CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CCC2=O)C(C)C)cc1)C(C)C IEDXPSOJFSVCKU-HOKPPMCLSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000980 acid dye Substances 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 208000025751 alpha chain disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 208000021780 appendiceal neoplasm Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 108010044540 auristatin Proteins 0.000 description 1
- 230000007325 autophagic turnover Effects 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 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 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 201000000135 breast papillary carcinoma Diseases 0.000 description 1
- 229960000455 brentuximab vedotin Drugs 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 239000000298 carbocyanine Substances 0.000 description 1
- 125000000837 carbohydrate group Chemical group 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000010001 cellular homeostasis Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- OEUUFNIKLCFNLN-LLVKDONJSA-N chembl432481 Chemical compound OC(=O)[C@@]1(C)CSC(C=2C(=CC(O)=CC=2)O)=N1 OEUUFNIKLCFNLN-LLVKDONJSA-N 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000002038 chemiluminescence detection Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- QPAKKWCQMHUHNI-GQIQPHNSSA-N chlorotoxin Chemical compound C([C@H]1C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]4CSSC[C@@H](C(N[C@@H](CCSC)C(=O)N5CCC[C@H]5C(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)CNC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC2=O)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC4=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N3)=O)NC(=O)[C@@H](N)CCSC)C1=CC=C(O)C=C1 QPAKKWCQMHUHNI-GQIQPHNSSA-N 0.000 description 1
- 229960005534 chlorotoxin Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 1
- 229960005061 crizotinib Drugs 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960000975 daunorubicin 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
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- BTNBMQIHCRIGOU-UHFFFAOYSA-N delta-tocotrienol Natural products CC(=CCCC(=CCCC(=CCCOC1(C)CCc2cc(O)cc(C)c2O1)C)C)C BTNBMQIHCRIGOU-UHFFFAOYSA-N 0.000 description 1
- 238000000326 densiometry Methods 0.000 description 1
- 229950008925 depatuxizumab mafodotin Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000001152 differential interference contrast microscopy Methods 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000019439 energy homeostasis Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 238000001952 enzyme assay Methods 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
- 210000003979 eosinophil Anatomy 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- 208000028653 esophageal adenocarcinoma Diseases 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 208000024519 eye neoplasm Diseases 0.000 description 1
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 229960003082 galactose Drugs 0.000 description 1
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 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 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 201000000284 histiocytoma Diseases 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229950004101 inotuzumab ozogamicin Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 208000020082 intraepithelial neoplasia Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 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 1
- 150000002505 iron Chemical class 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 201000002529 islet cell tumor Diseases 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 208000022013 kidney Wilms tumor Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229960004891 lapatinib Drugs 0.000 description 1
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- YAFQFNOUYXZVPZ-UHFFFAOYSA-N liproxstatin-1 Chemical compound ClC1=CC=CC(CNC=2C3(CCNCC3)NC3=CC=CC=C3N=2)=C1 YAFQFNOUYXZVPZ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000010859 live-cell imaging Methods 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 229950003526 lorvotuzumab mertansine Drugs 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 208000037829 lymphangioendotheliosarcoma Diseases 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000006674 lysosomal degradation Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 201000009020 malignant peripheral nerve sheath tumor Diseases 0.000 description 1
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 1
- 208000021937 marginal zone lymphoma Diseases 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 238000011177 media preparation Methods 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 230000006609 metabolic stress Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 208000026114 mu chain disease Diseases 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000002077 muscle cancer Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 208000001611 myxosarcoma Diseases 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 201000002120 neuroendocrine carcinoma Diseases 0.000 description 1
- 208000029974 neurofibrosarcoma Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 1
- 229960001346 nilotinib Drugs 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000004767 nitrides Chemical class 0.000 description 1
- 210000004882 non-tumor cell Anatomy 0.000 description 1
- 150000002843 nonmetals Chemical class 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000031787 nutrient reservoir activity Effects 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- 201000008106 ocular cancer Diseases 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 201000005443 oral cavity cancer Diseases 0.000 description 1
- 201000002740 oral squamous cell carcinoma Diseases 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 201000006958 oropharynx cancer Diseases 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 1
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 1
- YOURXVGYNVXQKT-UHFFFAOYSA-N oxacycloundecane-2,11-dione Chemical compound O=C1CCCCCCCCC(=O)O1 YOURXVGYNVXQKT-UHFFFAOYSA-N 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- BPUBBGLMJRNUCC-UHFFFAOYSA-N oxygen(2-);tantalum(5+) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[Ta+5].[Ta+5] BPUBBGLMJRNUCC-UHFFFAOYSA-N 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 208000022102 pancreatic neuroendocrine neoplasm Diseases 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 208000012111 paraneoplastic syndrome Diseases 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- QWYZFXLSWMXLDM-UHFFFAOYSA-M pinacyanol iodide Chemical compound [I-].C1=CC2=CC=CC=C2N(CC)C1=CC=CC1=CC=C(C=CC=C2)C2=[N+]1CC QWYZFXLSWMXLDM-UHFFFAOYSA-M 0.000 description 1
- 208000010626 plasma cell neoplasm Diseases 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 201000006037 primary mediastinal B-cell lymphoma Diseases 0.000 description 1
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 239000007320 rich medium Substances 0.000 description 1
- 229950000143 sacituzumab govitecan Drugs 0.000 description 1
- ULRUOUDIQPERIJ-PQURJYPBSA-N sacituzumab govitecan Chemical compound N([C@@H](CCCCN)C(=O)NC1=CC=C(C=C1)COC(=O)O[C@]1(CC)C(=O)OCC2=C1C=C1N(C2=O)CC2=C(C3=CC(O)=CC=C3N=C21)CC)C(=O)COCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCN(N=N1)C=C1CNC(=O)C(CC1)CCC1CN1C(=O)CC(SC[C@H](N)C(O)=O)C1=O ULRUOUDIQPERIJ-PQURJYPBSA-N 0.000 description 1
- 229960001548 salinomycin Drugs 0.000 description 1
- 235000019378 salinomycin Nutrition 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000004706 scrotum Anatomy 0.000 description 1
- 208000014956 scrotum Paget disease Diseases 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 125000005372 silanol group Chemical group 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- PBCFLUZVCVVTBY-UHFFFAOYSA-N tantalum pentoxide Inorganic materials O=[Ta](=O)O[Ta](=O)=O PBCFLUZVCVVTBY-UHFFFAOYSA-N 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide 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](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- QGHREAKMXXNCOA-UHFFFAOYSA-N thiophanate-methyl Chemical compound COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC QGHREAKMXXNCOA-UHFFFAOYSA-N 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 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
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 229960001612 trastuzumab emtansine Drugs 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 210000004981 tumor-associated macrophage Anatomy 0.000 description 1
- 230000002476 tumorcidal effect Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 208000037965 uterine sarcoma Diseases 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- 229960000653 valrubicin Drugs 0.000 description 1
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- GPXBXXGIAQBQNI-UHFFFAOYSA-N vemurafenib Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=CC(Cl)=CC=2)=C1F GPXBXXGIAQBQNI-UHFFFAOYSA-N 0.000 description 1
- 229960003862 vemurafenib Drugs 0.000 description 1
- 230000035899 viability Effects 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
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 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
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 208000028010 vulval Paget disease Diseases 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
- 239000011729 δ-tocotrienol Substances 0.000 description 1
- ODADKLYLWWCHNB-LDYBVBFYSA-N δ-tocotrienol Chemical compound OC1=CC(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 ODADKLYLWWCHNB-LDYBVBFYSA-N 0.000 description 1
- 235000019144 δ-tocotrienol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5115—Inorganic compounds
-
- 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
- A61K47/6921—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
- A61K47/6931—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
- A61K47/6935—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
-
- 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
- A61K47/6921—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- 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
- A61K47/56—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
- A61K47/6921—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6923—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 the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Abstract
Description
この出願は、2015年5月29日に出願された米国出願第62/168,636号および2016年1月20日に出願された米国出願第62/280,960号(これらの開示は、それらの全体が参考として本明細書に援用される)の利益を主張する。
この発明は、National Institutes of Health(NIH)/National Cancerによって付与された助成金1U54 CA199081−01、R01GM111350および1R01CA161280−01A1の下、政府の支援を受けてなされた。
したがって、適用特異的ナノ医薬(例えば、CおよびC’ドット)プラットフォームの設計を改善するために、濃度および時系列過程の変動が粒子ベースのプローブの内部移行後の消長にどのように影響を与えるか決定する必要性がまだある。
本開示がより容易に理解されるように、ある特定の用語を先ず下で定義する。以下の用語および他の用語の追加の定義は、本明細書全体で説明される。
異なるマクロファージサブセットは、がんにおける保護性または病原性のいずれかの役割と関連付けられている。典型的に活性化された、「炎症促進性」M1表現型マクロファージは、抗腫瘍免疫における役割を有し、腫瘍発生における保護性の役割を有する。これらのマクロファージは、腫瘍を死滅させる機構を活性化し、腫瘍関連マクロファージおよび骨髄由来の抑制性細胞の抑制性の活性に拮抗する。M1マクロファージは、Toll様受容体リガンド(リポ多糖など)およびインターフェロン−γによって活性化され、これは、ヘルパーT細胞サブタイプTH1の応答を増幅し、抗腫瘍応答における正のフィードバックループをもたらす。さらに、M1マクロファージは、中でも、炎症促進性サイトカインおよび誘導型一酸化窒素合成酵素を発現する。代替的に、活性化された、「消散促進性(pro−resolving)」マクロファージ(M2マクロファージ)は、抗炎症性機能を有し、創傷治癒を調節する。さらに、これらは、腫瘍特異性適応免疫応答を抑制し、腫瘍の増殖、浸潤、転移、間質リモデリングおよび血管新生を促進する。
MEFおよびHT1080細胞を、ペニシリン/ストレプトマイシン(Corning、Corning、NY)と共に10%ウシ胎仔血清(FBS、Sigma、St.Louis、MO)を補充したダルベッコ変法イーグル培地(DMEM)(MSKCC Media Preparation Facility)中で培養した。MCF10A細胞を、ペニシリン/ストレプトマイシンと共に5%ウマ血清(Atlanta Biologicals、Flowery Branch、GA)、20ng/ml EGF(Peprotech、Rocky Hill、NJ)、10μg/mlインスリン(Sigma)、0.5μg/mlヒドロコルチゾン(Sigma)、および100ng/mlコレラ毒素(Sigma)を補充したDMEM/F12(Gibco、Grand Island、NY)中で培養した。M21、BxPC3、H1650、および786−O細胞を、ペニシリン/ストレプトマイシンと共に10% FBSを補充したRPMI−1640(Gibco)中で培養した。SKOV3細胞を、ペニシリン/ストレプトマイシンと共に10% FBSを補充したマッコイ5a変法培地(Gibco)中で培養した。無アミノ酸培地を、熱不活化FBS(MEF、HT1080、M21、BxPC3、H1650、およびSKOV3細胞について)またはウマ血清(MCF10A細胞について)を4時間透析し、その後、MWCO3500透析管(21−152−9;Fisherbrand、Pittsburgh、PA)内のリン酸緩衝食塩水(PBS)中で4℃にて一晩インキュベートし、アミノ酸を用いずに調製した基本培地に添加することによって調製した。PRetro−Lamp1−GFPを、レトロウイルス形質導入によってM21細胞内に導入し、安定細胞株を、ピューロマイシン(2μg ml−1)を用いて選択した。
以下の試薬を示した濃度で使用した:コンカナマイシンA(ConA)(Sigma)100nM;SYTOXグリーン核酸染色剤(S7020;Invitrogen、Carlsbad、CA)5nM;フェロスタチン−1(Fer−1)(EMD Millipore、Billerica、MA)1μM;リプロクススタチン−1(Selleckchem)、in vitroおよびin vivoについてそれぞれ1μMおよび125mg/kg;デフェロキサミン(DFO)(Sigma)100μM;ブチルヒドロキシアニソール(BHA)(Sigma)50μM;アスコルビン酸(Asc酸)(Sigma)200μM;トロロクス(Sigma)100μM;N−アセチルシステイン(NAC)(Sigma)10mM;グルタチオン(GSH)(Sigma)5mM;TNFα(Sigma)100ng/ml;シクロヘキシミド(CHX)(Sigma)、ネクロトーシスおよびアポトーシスを誘導するために、それぞれ1μg/mlおよび50μg/ml;zVAD(Sigma)20μM;ネクロスタチン−1(Sigma)30μM;ブチオニンスルホキシミン(BSO)(Sigma)400μM;クエン酸鉄アンモニウム(FAC)(Sigma、F5879)400μM;エラスチン(Sigma)、5μM、C11−BODIPY(581/591)2μM(Invitrogen)。試薬は、ConAを例外として生物学的アッセイの開始時に培養物に添加し、ConAは、ウエスタンブロッティングのための溶解の1時間前に添加した。
二重アミノヘキサン酸(Ahx2)脂肪族リンカーおよびN−Ac−Cysを有する改変メラノコルチン−1受容体標的化ペプチドRe(Arg11)CCMSHを、標準的な固相Fmocペプチド化学を使用して合成した。レニウム環化αMSHペプチド類似体、Ac−Cys1−(Ahx)2−dLys2−Re[Cys−Cys−Glu−His−dPhe−Arg−Trp−Cys]−Arg−Pro−Val−NH2を、LCQ FLEETイオントラップ質量分析計(Thermo Fisher Scientific)とカップリングしたBeckman Coulter高速液体クロマトグラフィー(HPLC)システムで分析および精製し、凍結乾燥によって最終的に回収した。
αMSHは、神経免疫モジュレーターであり、その受容体、MC1−Rは、マクロファージ上に存在する。ある特定の実施形態では、αMSHペプチドをナノ粒子(例えば、C’ドット)に付着させる。ある特定の実施形態では、α−MSH−PEG−C’ドットを組み合わせ療法に使用する。例えば、α−MSH−PEG−C’ドットは、フェロトーシスを誘導し、αMSHペプチドを介して免疫調節をもたらす。
細胞をこすり取って氷冷RIPA緩衝液(プロテアーゼ阻害剤カクテルを含む、pH7.4の50mMのTris、150mMのNaCl、2mMのEDTA、1% NP40、0.1% SDS)中に入れ、氷上で10分間溶解させた。次いで溶解物を、15,870gで4℃にて20分間遠心分離し、タンパク質をBCAアッセイ(Pierce、Waltham、MA)によって定量化した。試料を、15%ポリアクリルアミドSDS−PAGEゲルで分離し、ポリビニルジフルオリド膜に移し、これを、TBSTおよび5% BSAでブロックし、ブロッキング緩衝液中に希釈した一次抗体(抗LC3A/B(4108;Cell Signaling、Danvers、MA)、抗FTH1(3998;Cell Signaling)、および抗アクチン(A1978;Sigma))と共に4℃で一晩インキュベートした。ブロットを、西洋わさびペルオキシダーゼにコンジュゲートした二次抗体と共にインキュベートし、タンパク質を、高感度化学発光検出(Invitrogen)を使用して検出した。デンシトメトリー分析を、ImageJソフトウェア(NIH)を使用して実行した。
細胞をガラス底皿(MatTek、Ashland、MA)上に蒔いた。一晩および蛍光および微分干渉コントラスト(DIC)画像を、Nikon TI−E倒立顕微鏡、CoolSNAP HQ2 CCD(電荷結合素子)カメラ(Photometrics、Tucson、AZ)を使用して示した時間にわたって30分毎に取得した。生細胞インキュベーションチャンバーにより、細胞を37℃および5%CO2で維持した。NIS Elementsソフトウェア(Nikon、Melville、NY)を使用した。細胞生存、死、および増殖を含めた細胞運命を手作業で定量化し、NIS ElementsソフトウェアおよびImage Jを使用して処理した。
グルタチオン測定のために、HT−1080細胞を6cm細胞培養皿上に蒔き、無アミノ酸DMEM+10%透析済みFBS中で、15μMのα−MSHタグ付きナノ粒子と共にインキュベートし、死の予測時間のおよそ2時間前に回収した。対照として、細胞を、完全または無アミノ酸DMEM 3部およびH2O 1部のミックス、または完全培地中100μMのBSOで処置した。細胞を冷PBSで3回洗浄し、冷溶解緩衝液50μL中で細胞擦過によって回収した。タンパク質濃度を、BCAアッセイを使用して測定し、試料体積を、それぞれが同じ最終タンパク質濃度を有するように調整した。製造者の指示に従って、全グルタチオンを、グルタチオンアッセイキット(Cayman Chemicals、703002)を使用して測定し、還元型グルタチオンを、QuantiChrom(商標)グルタチオンアッセイキット(BioAssay Systems、DIGT−250)を使用して測定した。
細胞を、15μMのα−MSH−PEG−C’ドットを用いてまたは用いずに24時間処置し、次いでH2DCFDA(25μM)またはC11−BODIPY(581/591)(2μM)(共にInvitrogen製)を補充したハンクス平衡塩溶液(HBSS)(Gibco)500μL中に回収および再懸濁し、37℃で15分間インキュベートした。次いで、細胞を新鮮なHBSS 500μL中に再懸濁し、フローサイトメーター(MoFlo、Beckman Coulter)のFL1チャネルを使用して分析した。データは、条件1つ当たり最低10,000細胞から収集した。
C’ドットの鉄ローディング能力測定について、α−MSH−PEG−C’ドット(60μM)50μLを鉄含有培地(8.6μM)150μLまたは一連の鉄(Fe3+)濃度(2μM〜2mM、表1)にわたって調製したFeCl3溶液150μLに添加した。溶液を室温で48時間回転させ(160rpm)、その後、PD−10カラムを使用してC’ドットから遊離鉄を分離し、水で溶出した。細胞試料を、培地中で粒子と共に、および粒子無しで48時間インキュベートした後、遠心分離し、ペレット化し、3回洗浄した後、リン酸緩衝食塩溶液中に再懸濁した。鉄測定値(パーツパービリオン、ppb)を、鉄ローディング能力と共に、マイクロ波プラズマ−原子発光分光法を使用して決定した。鉄ローディング能力は、精製粒子に曝露されたC’ドット(または細胞)中の鉄の量を精製前に測定した初期の鉄の合計量によって除し、100を乗じた比として計算した。すべての実験は、三連で実施した。
GPX4活性アッセイ
GPX4比活性アッセイは、Roveriおよび共同研究者によって実施された。簡単に言えば、凍結細胞ペレットを、溶解緩衝液(100mMのKH2PO4/K2HPO4、pH7.4、1mMのEDTA、150mMのKCl、0.1% CHAPS、3mMのβ−メルカプトエタノール、およびプロテアーゼ阻害剤カクテル)100μL中に再懸濁し、50回乳棒でストロークすることによってホモジナイズした。試料を氷上で15分間インキュベートし、細胞残渣を遠心分離(20000gおよび10分、4℃)によって除去した。ホモジナイズされた細胞由来の上清50μLを使用して、20μMホスファチジルコリンヒドロペルオキシド(PCOOH)の存在下で、アッセイ緩衝液(5mMのEDTA、0.1% Triton X、3mMのGSH、200μMのNADPH、および0.6U/mlグルタチオン還元酵素を含有する100mMのTrisHCl pH7.8)1ml中で酵素活性を測定した。GPX4活性を、SpectraMaxプレートリーダー(Molecular Device GmbH)で340nmの吸光度の低下によって検出可能なNADPHのグルタチオン還元酵素依存性消費量によって決定した。試料中のタンパク質含有量を、比色660nm Pierce Protein Assay法(Pierce、Waltham、MA)によって決定した。
すべての動物実験は、Memorial Sloan−Kettering Cancer Centerの施設内動物管理使用委員会によって承認されたプロトコールによって、かつ動物愛護のNIH指針に従って実施した。ヒトメラノーマ(M21)異種移植片を、免疫不全雄SCID/Beige(C.B−17/IcrHsd−PrkdcscidLystbg−J)マウス(生後6〜8週;Harlan Laboratories、South Easton、MA)の剃毛した側腹部に生成した。ヒト肉腫HT1080および786−O側腹部異種移植片(約2×106細胞/100μl)を、静脈内粒子注射の同じモデルを使用してさらに生成した。45〜75mm3の平均初期腫瘍体積を、すべての実験に使用した。
血清補充培地中で培養した500万個のM21細胞を、粒子曝露の2日後に(n=3)または曝露無しで(n=3)、23ゲージトロカール針を使用してマウスの右側腹部内に皮下移植して、メラノーマ異種移植片を確立した。後続の試験において、マウスを、2つの異なる処置群のうちの1つに割り当てて、10日の期間にわたって3回(すなわち、0、4、7日目に)投与した高濃度(60μM)のi.v.注射α−MSH−PEG−C’ドット(n=5匹のマウス;200μl)に対するHT−1080および786−O腫瘍の応答を評価した。対照HT−1080および786−Oマウス(n=3)に、0.9%食塩水ビヒクルを同じ時点に投与した。第3の処置試験では、HT−1080マウスを、2つの群のうちの1つに割り当てて、10日の期間にわたって、単独での、またはリプロクススタチン1を腹腔内投与した後の(n=3匹のマウス、125mg/kg)、3回の高濃度用量(60μM)のi.v.注射α−MSH−PEG−C’ドット(n=3匹のマウス;200μl)に対する応答を評価した。腫瘍サイズは、処置の間隔にわたってカリパスを使用して測定した。すべてのマウスを、腫瘍細胞接種の部位において触診によって検査し、病的状態または死亡の徴候についての腫瘍成長試験が終結するまで毎日観察した。腫瘍体積(V;4/3・π・d1 2・d2/8)を計算するのに使用される腫瘍の2つの直交する直径(d1≦d2)を、細胞を注射した後毎日カリパスで測定した。
動物を、イソフルランを使用して麻酔し、全身光学蛍光イメージングを取得して腫瘍部位におけるナノ粒子蛍光を特定した。マウスを、製造者の推奨に従って選択したCy5蛍光(励起650nm、発光680nm)およびバックグラウンド蛍光(励起465nm、発光600nm)のためのブロックおよびフィルターと共にIVISスペクトル光子計数装置光学イメージングシステム(Xenogen、Alameda、CA)を使用して0.1〜1秒間走査した。蛍光バックグラウンドを、製造者の指示に従って同様に差し引いた。蛍光信号を、放射効率((光子/秒/cm2/sr)/(mW/cm2)として報告した。
in vivoイメージング試験の終結直後に、HT−1080および786−O雄および雌マウスを、CO2吸入によって安楽死させ、代表的な粒子曝露(n=2)および対照(n=1)腫瘍ならびに肝臓および腎臓検体を剖検で切り取った。血液検体を完全血球算定および血清化学のためにさらに得た。切り取った腫瘍、肝臓、および腎臓を、10%中性緩衝ホルマリン中で24時間固定し、アルコールおよびキシレンで処理し、パラフィン中に包埋し、5ミクロンの厚さで切片にし、ヘマトキシリンおよびエオシン(H&E)で染色した。追加の切片を、Mac−2(pH6.0緩衝液中の熱誘導エピトープ回復[HIER]後に1:100の濃度で施用した一次抗体Cedarlane CL8942B)、ミエロペルオキシダーゼ(Dako A0398、1:1000、HIER pH6.0)、切断カスパーゼ−3(Cell Signaling Technology 9661、1:250、HIER pH6.0)、およびKi−67(Abcam ab16667、1:100、HIER pH9.0)について免疫組織化学によって染色した。Mac−2染色を、アビジン−ビオチン検出システム(Vectastain ABC Elite Kit、Vector Laboratories、PK−6100)を用いて手作業で実施した。他の染色は、Bond Polymer Refine検出キット(Leica Biosystem DS9800)を使用してLeica Bond RX自動染色機で実施した。腫瘍切片は、以前に記載したTUNEL法によっても染色した。すべてのスライドは、有資格獣医病理学者によって検査された。
腫瘍血管分布を、Leica Bond RX自動染色プラットフォーム(Leica Biosystems)で、CD31について免疫組織化学によりHT−1080腫瘍を染色することによって評価した。pH9.0で熱誘導エピトープ回復をした後、一次抗体(ラットモノクローナル、カタログ#DIA−310;Dianova)を1:250の濃度で施用し、その後ポリマー検出システム(Novocastra Bond Polymer Refine Detection、Leica Biosystems)を利用した。
体積−時間プロファイルを、一般化推定方程式手法によって計算したロバストな標準誤差を使用して、2つの処置群間で比較した。フェロトーシスに対する薬理学的阻害剤、リプロクススタチン−1を用いた、および用いない粒子処置腫瘍成長プロファイルを、線形モデルを使用して比較した。データの長軸方向のアスペクト(longitudinal aspect)を、一般化推定方程式を使用して考慮に入れた。統計的有意性は、P<0.05であるとされた。
例えば、本発明の実施形態において、以下の項目が提供される。
(項目1)
腫瘍組織における十分に高い濃度での蓄積のためにナノ粒子を投与し、フェロトーシス(例えば、鉄依存性壊死または反応性酸素種依存性壊死を含むフェロトーシス細胞死)を誘導するステップ
を含む、被験体の処置方法。
(項目2)
前記ナノ粒子が極小ナノ粒子(例えば、Cドット、例えばC’ドット)を含む、項目1に記載の方法。
(項目3)
前記高い濃度が、1μMを超える、例えば15μMを超える、例えば60μMを超える、項目1または2に記載の方法。
(項目4)
前記高い濃度が、前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)、前記項目のいずれか一項に記載の方法。
(項目5)
前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)、前記項目のいずれか一項に記載の方法。
(項目6)
前記腫瘍組織がフェロトーシスの誘導に感作されている、前記項目のいずれか一項に記載の方法。
(項目7)
腫瘍組織への輸送(および/または腫瘍組織における蓄積)のために薬物を投与するステップ;および
(フェロトーシスを誘導するために)前記腫瘍組織における十分に高い濃度での蓄積のためにナノ粒子を投与するステップ
を含む、被験体の組み合わせ処置の方法。
(項目8)
前記薬物が化学療法剤(例えば、TAS−102)を含む、項目7に記載の方法。
(項目9)
前記ナノ粒子が極小ナノ粒子(例えば、Cドット、例えばC’ドット)を含む、項目7または8に記載の方法。
(項目10)
前記高い濃度が、1μMを超える、例えば15μMを超える、例えば60μMを超える、項目7〜9のいずれか一項に記載の方法。
(項目11)
前記高い濃度が、前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である(例えば、前記高い濃度は、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子はシリカをベースとしており、例えば、前記ナノ粒子はCドットまたはC’ドットである)、項目7〜9のいずれか一項に記載の方法。
(項目12)
前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)、項目7〜11のいずれか一項に記載の方法。
(項目13)
前記腫瘍組織がフェロトーシスの誘導に感作されている、項目7〜11のいずれか一項に記載の方法。
(項目14)
前記薬物を投与するステップおよび前記ナノ粒子を投与するステップが、前記薬物および前記ナノ粒子の両方を含む組成物を投与することによって達成される、項目7〜13のいずれか一項に記載の方法。
(項目15)
前記組成物がナノ粒子薬物コンジュゲートを含む、項目7〜14のいずれか一項に記載の方法。
(項目16)
腫瘍組織(例えば、前立腺がん組織)からホルモンを欠乏させるステップ;および
前記腫瘍組織における十分に高い濃度での蓄積のためにナノ粒子を投与し、フェロトーシスを誘導するステップ
を含む、被験体の組み合わせ処置の方法。
(項目17)
前記腫瘍組織が去勢(例えば、化学的去勢)を経てホルモンを欠乏させる、項目16に記載の方法。
(項目18)
前記ナノ粒子が極小ナノ粒子(例えば、Cドット、例えばC’ドット)を含む、項目16または17に記載の方法。
(項目19)
前記高い濃度が、1μMを超える、例えば15μMを超える、例えば60μMを超える、項目16〜18のいずれか一項に記載の方法。
(項目20)
前記高い濃度が、前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である(例えば、前記高い濃度は、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子はシリカをベースとしており、例えば、前記ナノ粒子はCドットまたはC’ドットである)、項目16〜18のいずれか一項に記載の方法。
(項目21)
前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)、項目16〜20のいずれか一項に記載の方法。
(項目22)
前記腫瘍組織がフェロトーシスの誘導に感作されている、項目16〜20のいずれか一項に記載の方法。
(項目23)
前記腫瘍組織が、腎臓、前立腺、メラノーマ、膵臓、肺、線維肉腫、乳房、脳、卵巣および結腸腫瘍組織からなる群より選択される、前記項目のいずれか一項に記載の方法。
(項目24)
前記膵臓腫瘍組織がBxPC3細胞を含む、前記項目のいずれか一項に記載の方法。
(項目25)
前記肺腫瘍組織がH1650細胞を含む、前記項目のいずれか一項に記載の方法。
(項目26)
前記ナノ粒子が15nm以下の平均直径を有する、前記項目のいずれか一項に記載の方法。
(項目27)
前記ナノ粒子が10nm以下の平均直径を有する、前記項目のいずれか一項に記載の方法。
(項目28)
前記ナノ粒子が約5nmから約7nm(例えば、約6nm)の平均直径を有する、前記項目のいずれか一項に記載の方法。
(項目29)
前記ナノ粒子が1から20個の標的化部分を含み、前記標的化部分が腫瘍細胞上の受容体に結合する(例えば、前記ナノ粒子が、15nm以下、例えば10nm以下、例えば約5nmから約7nm、例えば約6nmの平均直径を有する)、前記項目のいずれか一項に記載の方法。
(項目30)
1から20個の前記標的化部分がアルファ−メラニン細胞刺激ホルモン(αMSH)を含む、前記項目のいずれか一項に記載の方法。
(項目31)
前記ナノ粒子が標的化部分(例えば、αMSH)を含む、前記項目のいずれか一項に記載の方法。
(項目32)
前記ナノ粒子が処置の過程にわたって複数回投与される、前記項目のいずれか一項に記載の方法。
(項目33)
処置の過程にわたって前記ナノ粒子を3または4日ごとに投与するステップをさらに含む、前記項目のいずれか一項に記載の方法。
(項目34)
投与される前記ナノ粒子に薬物(例えば、化学療法剤)が付着している、前記項目のいずれか一項に記載の方法。
(項目35)
前記薬物がリンカー部分を介して付着している(例えば、共有結合または非共有結合で付着している)、前記項目のいずれか一項に記載の方法。
(項目36)
がん処置および/または組織修復プロセス(例えば、創傷治癒)においてCドットの治療能力を増加させるために、薬物送達が、投与される前記ナノ粒子の天然の免疫調節特性と組み合わされる(例えば、前記ナノ粒子がα−MSH−PEG−C’ドットを含む、例えば、α−MSHが前記ナノ粒子の表面に結合している)(例えば、前記ナノ粒子が有機ポリマーコーティング(例えば、ポリエチレングリコール(PEG))を含む)、前記項目のいずれか一項に記載の方法。
(項目37)
被験体を処置する方法で使用するためのナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む組成物であって、
前記処置が、腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のために前記被験体の腫瘍組織に前記組成物を送達し、フェロトーシスを誘導することを含む(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)、組成物。
(項目38)
療法で使用するためにフェロトーシスを誘導するために、腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のためのナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)組成物。
(項目39)
被験体を処置する方法で使用するための薬物(例えば、化学療法剤、例えばTAS102)を含む第1の組成物およびナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む第2の組成物であって、
前記処置が、
前記被験体の腫瘍組織への輸送(および/または腫瘍組織における蓄積)のために前記第1の組成物を送達すること;ならびに
腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のために前記被験体の前記腫瘍組織に前記第2の組成物を送達し(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)、フェロトーシスを誘導すること
を含む、第1の組成物および第2の組成物。
(項目40)
療法で使用するための、フェロトーシスを誘導するために、被験体の腫瘍組織への輸送(および/または腫瘍組織における蓄積)のための薬物(例えば、任意の化学療法剤、例えばTAS102)を含む第1の組成物;
および腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のためのナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む第2の組成物(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)。
(項目41)
被験体を処置する方法で使用するためのナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む組成物であって、
前記処置が、
前記被験体の腫瘍組織(例えば、前立腺組織)からホルモン(例えば、去勢(例えば、化学的去勢)を経て)を欠乏させること;および
腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のために前記被験体の前記腫瘍組織に前記組成物を送達し(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)、フェロトーシスを誘導すること
を含む、組成物。
Claims (41)
- 腫瘍組織における十分に高い濃度での蓄積のためにナノ粒子を投与し、フェロトーシス(例えば、鉄依存性壊死または反応性酸素種依存性壊死を含むフェロトーシス細胞死)を誘導するステップ
を含む、被験体の処置方法。 - 前記ナノ粒子が極小ナノ粒子(例えば、Cドット、例えばC’ドット)を含む、請求項1に記載の方法。
- 前記高い濃度が、1μMを超える、例えば15μMを超える、例えば60μMを超える、請求項1または2に記載の方法。
- 前記高い濃度が、前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)、前記請求項のいずれか一項に記載の方法。
- 前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)、前記請求項のいずれか一項に記載の方法。
- 前記腫瘍組織がフェロトーシスの誘導に感作されている、前記請求項のいずれか一項に記載の方法。
- 腫瘍組織への輸送(および/または腫瘍組織における蓄積)のために薬物を投与するステップ;および
(フェロトーシスを誘導するために)前記腫瘍組織における十分に高い濃度での蓄積のためにナノ粒子を投与するステップ
を含む、被験体の組み合わせ処置の方法。 - 前記薬物が化学療法剤(例えば、TAS−102)を含む、請求項7に記載の方法。
- 前記ナノ粒子が極小ナノ粒子(例えば、Cドット、例えばC’ドット)を含む、請求項7または8に記載の方法。
- 前記高い濃度が、1μMを超える、例えば15μMを超える、例えば60μMを超える、請求項7〜9のいずれか一項に記載の方法。
- 前記高い濃度が、前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である(例えば、前記高い濃度は、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子はシリカをベースとしており、例えば、前記ナノ粒子はCドットまたはC’ドットである)、請求項7〜9のいずれか一項に記載の方法。
- 前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)、請求項7〜11のいずれか一項に記載の方法。
- 前記腫瘍組織がフェロトーシスの誘導に感作されている、請求項7〜11のいずれか一項に記載の方法。
- 前記薬物を投与するステップおよび前記ナノ粒子を投与するステップが、前記薬物および前記ナノ粒子の両方を含む組成物を投与することによって達成される、請求項7〜13のいずれか一項に記載の方法。
- 前記組成物がナノ粒子薬物コンジュゲートを含む、請求項7〜14のいずれか一項に記載の方法。
- 腫瘍組織(例えば、前立腺がん組織)からホルモンを欠乏させるステップ;および
前記腫瘍組織における十分に高い濃度での蓄積のためにナノ粒子を投与し、フェロトーシスを誘導するステップ
を含む、被験体の組み合わせ処置の方法。 - 前記腫瘍組織が去勢(例えば、化学的去勢)を経てホルモンを欠乏させる、請求項16に記載の方法。
- 前記ナノ粒子が極小ナノ粒子(例えば、Cドット、例えばC’ドット)を含む、請求項16または17に記載の方法。
- 前記高い濃度が、1μMを超える、例えば15μMを超える、例えば60μMを超える、請求項16〜18のいずれか一項に記載の方法。
- 前記高い濃度が、前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である(例えば、前記高い濃度は、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子はシリカをベースとしており、例えば、前記ナノ粒子はCドットまたはC’ドットである)、請求項16〜18のいずれか一項に記載の方法。
- 前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)、請求項16〜20のいずれか一項に記載の方法。
- 前記腫瘍組織がフェロトーシスの誘導に感作されている、請求項16〜20のいずれか一項に記載の方法。
- 前記腫瘍組織が、腎臓、前立腺、メラノーマ、膵臓、肺、線維肉腫、乳房、脳、卵巣および結腸腫瘍組織からなる群より選択される、前記請求項のいずれか一項に記載の方法。
- 前記膵臓腫瘍組織がBxPC3細胞を含む、前記請求項のいずれか一項に記載の方法。
- 前記肺腫瘍組織がH1650細胞を含む、前記請求項のいずれか一項に記載の方法。
- 前記ナノ粒子が15nm以下の平均直径を有する、前記請求項のいずれか一項に記載の方法。
- 前記ナノ粒子が10nm以下の平均直径を有する、前記請求項のいずれか一項に記載の方法。
- 前記ナノ粒子が約5nmから約7nm(例えば、約6nm)の平均直径を有する、前記請求項のいずれか一項に記載の方法。
- 前記ナノ粒子が1から20個の標的化部分を含み、前記標的化部分が腫瘍細胞上の受容体に結合する(例えば、前記ナノ粒子が、15nm以下、例えば10nm以下、例えば約5nmから約7nm、例えば約6nmの平均直径を有する)、前記請求項のいずれか一項に記載の方法。
- 1から20個の前記標的化部分がアルファ−メラニン細胞刺激ホルモン(αMSH)を含む、前記請求項のいずれか一項に記載の方法。
- 前記ナノ粒子が標的化部分(例えば、αMSH)を含む、前記請求項のいずれか一項に記載の方法。
- 前記ナノ粒子が処置の過程にわたって複数回投与される、前記請求項のいずれか一項に記載の方法。
- 処置の過程にわたって前記ナノ粒子を3または4日ごとに投与するステップをさらに含む、前記請求項のいずれか一項に記載の方法。
- 投与される前記ナノ粒子に薬物(例えば、化学療法剤)が付着している、前記請求項のいずれか一項に記載の方法。
- 前記薬物がリンカー部分を介して付着している(例えば、共有結合または非共有結合で付着している)、前記請求項のいずれか一項に記載の方法。
- がん処置および/または組織修復プロセス(例えば、創傷治癒)においてCドットの治療能力を増加させるために、薬物送達が、投与される前記ナノ粒子の天然の免疫調節特性と組み合わされる(例えば、前記ナノ粒子がα−MSH−PEG−C’ドットを含む、例えば、α−MSHが前記ナノ粒子の表面に結合している)(例えば、前記ナノ粒子が有機ポリマーコーティング(例えば、ポリエチレングリコール(PEG))を含む)、前記請求項のいずれか一項に記載の方法。
- 被験体を処置する方法で使用するためのナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む組成物であって、
前記処置が、腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のために前記被験体の腫瘍組織に前記組成物を送達し、フェロトーシスを誘導することを含む(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)、組成物。 - 療法で使用するためにフェロトーシスを誘導するために、腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のためのナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)組成物。
- 被験体を処置する方法で使用するための薬物(例えば、化学療法剤、例えばTAS102)を含む第1の組成物およびナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む第2の組成物であって、
前記処置が、
前記被験体の腫瘍組織への輸送(および/または腫瘍組織における蓄積)のために前記第1の組成物を送達すること;ならびに
腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のために前記被験体の前記腫瘍組織に前記第2の組成物を送達し(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)、フェロトーシスを誘導すること
を含む、第1の組成物および第2の組成物。 - 療法で使用するための、フェロトーシスを誘導するために、被験体の腫瘍組織への輸送(および/または腫瘍組織における蓄積)のための薬物(例えば、任意の化学療法剤、例えばTAS102)を含む第1の組成物;
および腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のためのナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む第2の組成物(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)。 - 被験体を処置する方法で使用するためのナノ粒子(例えば、極小ナノ粒子、例えばCドット、例えばC’ドット)を含む組成物であって、
前記処置が、
前記被験体の腫瘍組織(例えば、前立腺組織)からホルモン(例えば、去勢(例えば、化学的去勢)を経て)を欠乏させること;および
腫瘍組織における十分に高い濃度(例えば、1μMを超える、例えば15μMを超える、例えば60μMを超える)での蓄積のために前記被験体の前記腫瘍組織に前記組成物を送達し(例えば、前記高い濃度が前記腫瘍組織において0.18μMから1.8μMの範囲内の局所濃度である)(例えば、前記高い濃度が、少なくとも0.18μM、少なくとも0.3μM、少なくとも0.4μM、少なくとも0.5μMまたは少なくとも0.6μMの前記腫瘍組織における局所濃度であり;例えば、前記ナノ粒子がシリカをベースとしており、例えば、前記ナノ粒子がCドットまたはC’ドットである)(例えば、前記腫瘍組織が、十分にアミノ酸が欠乏している(または代謝的に欠乏している)か、またはその他の点でフェロトーシスの誘導に対して感受性である)、フェロトーシスを誘導すること
を含む、組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2021180243A JP7263485B2 (ja) | 2015-05-29 | 2021-11-04 | フェロトーシスを介して栄養欠乏がん細胞の細胞死を誘導するための極小ナノ粒子を使用する処置方法 |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562168636P | 2015-05-29 | 2015-05-29 | |
US62/168,636 | 2015-05-29 | ||
US201662280960P | 2016-01-20 | 2016-01-20 | |
US62/280,960 | 2016-01-20 | ||
PCT/US2016/034351 WO2016196201A1 (en) | 2015-05-29 | 2016-05-26 | Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021180243A Division JP7263485B2 (ja) | 2015-05-29 | 2021-11-04 | フェロトーシスを介して栄養欠乏がん細胞の細胞死を誘導するための極小ナノ粒子を使用する処置方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018516249A true JP2018516249A (ja) | 2018-06-21 |
JP2018516249A5 JP2018516249A5 (ja) | 2019-06-13 |
JP6974178B2 JP6974178B2 (ja) | 2021-12-01 |
Family
ID=56134596
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017560717A Active JP6974178B2 (ja) | 2015-05-29 | 2016-05-26 | フェロトーシスを介して栄養欠乏がん細胞の細胞死を誘導するための極小ナノ粒子を使用する処置方法 |
JP2021180243A Active JP7263485B2 (ja) | 2015-05-29 | 2021-11-04 | フェロトーシスを介して栄養欠乏がん細胞の細胞死を誘導するための極小ナノ粒子を使用する処置方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021180243A Active JP7263485B2 (ja) | 2015-05-29 | 2021-11-04 | フェロトーシスを介して栄養欠乏がん細胞の細胞死を誘導するための極小ナノ粒子を使用する処置方法 |
Country Status (10)
Country | Link |
---|---|
US (3) | US10736972B2 (ja) |
EP (1) | EP3302568B1 (ja) |
JP (2) | JP6974178B2 (ja) |
KR (1) | KR20180012299A (ja) |
CN (2) | CN108377643B (ja) |
AU (1) | AU2016271040A1 (ja) |
BR (1) | BR112017024328A2 (ja) |
CA (1) | CA2985126A1 (ja) |
HK (1) | HK1253536A1 (ja) |
WO (1) | WO2016196201A1 (ja) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK2449379T3 (en) | 2009-07-02 | 2017-08-28 | Sloan-Kettering Inst For Cancer Res | FLUORESCING SILICA-BASED NANOPARTICLES |
BR112015020782A2 (pt) | 2013-03-15 | 2017-10-10 | Univ Cornell | nanopartículas à base de sílica multimodal |
CN106659797B (zh) | 2014-05-29 | 2021-04-27 | 纪念斯隆-凯特琳癌症中心 | 纳米粒子药物结合物 |
AU2016271040A1 (en) | 2015-05-29 | 2017-11-23 | Cornell University | Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis |
JP7455510B2 (ja) * | 2016-04-29 | 2024-03-26 | メモリアル スローン-ケタリング キャンサー センター | 悪性脳腫瘍における標的化粒子の浸透、分布および応答のための組成物及び方法 |
US20200138829A1 (en) * | 2017-05-24 | 2020-05-07 | Ferro Therapeutics, Inc. | Methods of cancer treatment |
WO2018217528A1 (en) * | 2017-05-25 | 2018-11-29 | Memorial Sloan Kettering Cancer Center | Ultrasmall nanoparticles labeled with zirconium-89 and methods thereof |
WO2019006005A2 (en) * | 2017-06-28 | 2019-01-03 | The Regents Of The University Of California | METHODS AND COMPOSITIONS FOR THE TREATMENT OF MELANOMA |
US20200383943A1 (en) * | 2017-12-04 | 2020-12-10 | Memorial Sloan Kettering Cancer Center | Methods of cancer treatment via regulated ferroptosis |
WO2019151813A1 (ko) | 2018-01-31 | 2019-08-08 | 주식회사 엘지화학 | 음극 활물질, 이를 포함하는 음극 및 리튬 이차전지 |
WO2019168999A1 (en) | 2018-02-28 | 2019-09-06 | Ferro Therapeutics, Inc. | Compounds with ferroptosis inducing activity and methods of their use |
WO2019200343A1 (en) * | 2018-04-13 | 2019-10-17 | The Wistar Institute Of Anatomy And Biology | S6k2 blockade perturbs redox balance and fatty acid metabolism, leading to oxidative cell death in mapk inhibitor resistant cancers |
WO2019212945A1 (en) * | 2018-05-02 | 2019-11-07 | Memorial Sloan Kettering Cancer Center | Nanotherapeutic systems and methods using particle-driven photodynamic therapy (pdt) |
WO2020077361A1 (en) * | 2018-10-12 | 2020-04-16 | The General Hospital Corporation | Compounds and methods of their use |
US20220193275A1 (en) * | 2018-12-17 | 2022-06-23 | Memorial Sloan Kettering Cancer Center | Inducing favorable effects on tumor microenvironment via administration of nanoparticle compositions |
US11040964B2 (en) | 2019-02-27 | 2021-06-22 | Ferro Therapeutics, Inc. | Compounds and methods of use |
AU2021370647A1 (en) | 2020-10-27 | 2023-06-08 | Elucida Oncology, Inc. | Folate receptor targeted nanoparticle drug conjugates and uses thereof |
CN112274495B (zh) * | 2020-10-31 | 2022-05-03 | 郑州大学 | 一种h2o2自供型过氧化钙负载姜黄素纳米粒的制备方法及其应用 |
WO2022271619A1 (en) * | 2021-06-21 | 2022-12-29 | Memorial Sloan-Kettering Cancer Center | Nanoparticle-mediated enhancement of immunotherapy to promote ferroptosis-induced cytotoxicity and antitumor immune responses |
WO2023023288A1 (en) * | 2021-08-19 | 2023-02-23 | Arpeggio Biosciences, Inc. | Small molecule modulators of ferroptosis |
US11541116B1 (en) | 2022-01-07 | 2023-01-03 | Kojin Therapeutics, Inc. | Methods and compositions for inducing ferroptosis in vivo |
CN115120595B (zh) * | 2022-08-02 | 2023-06-30 | 广西医科大学第一附属医院 | Liproxstatin-1在制备防治白血病的药物中的应用和其药物组合物 |
CN116270624A (zh) * | 2023-02-14 | 2023-06-23 | 中山大学肿瘤防治中心(中山大学附属肿瘤医院、中山大学肿瘤研究所) | Tubastatin A的新应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130039848A1 (en) * | 2009-07-02 | 2013-02-14 | Cornell University | Fluorescent silica-based nanoparticles |
Family Cites Families (78)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3870791A (en) | 1972-04-24 | 1975-03-11 | Heskel M Haddad | Solid state ophthalmic medication delivery method |
US3867519A (en) | 1972-04-27 | 1975-02-18 | Alza Corp | Bioerodible drug delivery device |
US4051842A (en) | 1975-09-15 | 1977-10-04 | International Medical Corporation | Electrode and interfacing pad for electrical physiological systems |
DE2626348C3 (de) | 1976-06-11 | 1980-01-31 | Siemens Ag, 1000 Berlin Und 8000 Muenchen | Implantierbare Dosiereinrichtung |
US4136177A (en) | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Xanthan gum therapeutic compositions |
US4255415A (en) | 1978-11-22 | 1981-03-10 | Schering Corporation | Polyvinyl alcohol ophthalmic gel |
US4383529A (en) | 1980-11-03 | 1983-05-17 | Wescor, Inc. | Iontophoretic electrode device, method and gel insert |
US4931279A (en) | 1985-08-16 | 1990-06-05 | Bausch & Lomb Incorporated | Sustained release formulation containing an ion-exchange resin |
US4688506A (en) | 1985-09-03 | 1987-08-25 | Breems Martinus Van | Boat sail control system |
US4788603A (en) | 1985-10-19 | 1988-11-29 | Fuji Photo Film Co., Ltd. | Camera for sequentially photographing a subject using a reference optical system and a telescopic optical system |
US4812409A (en) | 1986-01-31 | 1989-03-14 | Eastman Kodak Company | Hydrolyzable fluorescent substrates and analytical determinations using same |
US4713224A (en) | 1986-03-31 | 1987-12-15 | The Boc Group, Inc. | One-step process for purifying an inert gas |
US4810636A (en) | 1986-12-09 | 1989-03-07 | Miles Inc. | Chromogenic acridinone enzyme substrates |
US4774339A (en) | 1987-08-10 | 1988-09-27 | Molecular Probes, Inc. | Chemically reactive dipyrrometheneboron difluoride dyes |
US5433896A (en) | 1994-05-20 | 1995-07-18 | Molecular Probes, Inc. | Dibenzopyrrometheneboron difluoride dyes |
US5274113A (en) | 1991-11-01 | 1993-12-28 | Molecular Probes, Inc. | Long wavelength chemically reactive dipyrrometheneboron difluoride dyes and conjugates |
US5248782A (en) | 1990-12-18 | 1993-09-28 | Molecular Probes, Inc. | Long wavelength heteroaryl-substituted dipyrrometheneboron difluoride dyes |
US5187288A (en) | 1991-05-22 | 1993-02-16 | Molecular Probes, Inc. | Ethenyl-substituted dipyrrometheneboron difluoride dyes and their synthesis |
US5776427A (en) | 1992-03-05 | 1998-07-07 | Board Of Regents, The University Of Texas System | Methods for targeting the vasculature of solid tumors |
US5830912A (en) | 1996-11-15 | 1998-11-03 | Molecular Probes, Inc. | Derivatives of 6,8-difluoro-7-hydroxycoumarin |
CN1147317C (zh) * | 1997-08-15 | 2004-04-28 | 赛福伦公司 | 含酪氨酸激酶抑制剂和化学阉割剂的组合物及其用于制药的用途 |
GB2330907A (en) | 1997-10-28 | 1999-05-05 | Applied Imaging Int Ltd | A karyotyper and methods for producing karyotypes |
ATE239801T1 (de) | 1998-01-22 | 2003-05-15 | Luminex Corp | Mikropartikel mit multiplen fluoreszenz-signalen |
US6254852B1 (en) | 1999-07-16 | 2001-07-03 | Dupont Pharmaceuticals Company | Porous inorganic targeted ultrasound contrast agents |
US7279150B2 (en) | 2002-01-24 | 2007-10-09 | Barnes-Jewish Hospital | Chelating agents with lipophilic carriers |
EP1482956A1 (en) | 2002-02-01 | 2004-12-08 | Vanderbilt University | Targeted drug delivery methods |
US8620410B2 (en) | 2002-03-12 | 2013-12-31 | Beth Israel Deaconess Medical Center | Multi-channel medical imaging system |
US20040101822A1 (en) | 2002-11-26 | 2004-05-27 | Ulrich Wiesner | Fluorescent silica-based nanoparticles |
US20080102036A1 (en) | 2003-06-04 | 2008-05-01 | Poss Kirtland G | Biocompatible Fluorescent Silicon Nanoparticles |
US20060173362A1 (en) | 2004-10-08 | 2006-08-03 | The Cleveland Clinic Foundation And Vanderbilt University | Methods of medical imaging using quantum dots |
US7653427B2 (en) | 2004-11-12 | 2010-01-26 | Intra-Medical Imaging LLC | Method and instrument for minimally invasive sentinel lymph node location and biopsy |
EP1861072A2 (en) | 2005-03-14 | 2007-12-05 | Massachusetts Institute Of Technology | Nanocells for diagnosis and treatment of diseases and disorders |
EP1957045A2 (en) | 2005-03-14 | 2008-08-20 | Board of Regents, The University of Texas System | Bioactive fus1 peptides and nanoprticle-polypeptide complexes |
US8084001B2 (en) | 2005-05-02 | 2011-12-27 | Cornell Research Foundation, Inc. | Photoluminescent silica-based sensors and methods of use |
WO2007053189A2 (en) | 2005-06-01 | 2007-05-10 | Northwestern University | Compositions and methods for altering immune function |
AU2006261917A1 (en) | 2005-06-24 | 2007-01-04 | The Trustees Of The University Of Pennsylvania | Radiolabeled-pegylation of ligands for use as imaging agents |
FR2888753B1 (fr) | 2005-07-21 | 2008-04-04 | Commissariat Energie Atomique | Vecteur cible avec fonction d'imagerie activable |
WO2007136413A2 (en) | 2005-12-22 | 2007-11-29 | Visen Medical, Inc. | Biocompatible fluorescent metal oxide nanoparticles |
WO2008044138A1 (en) | 2006-10-12 | 2008-04-17 | Syddansk Universitet | Optical nanosensor for detection of reactive oxygen species |
WO2008049118A2 (en) | 2006-10-19 | 2008-04-24 | The General Hospital Corporation | Apparatus and method for obtaining and providing imaging information associated with at least one portion of a sample and effecting such portion(s) |
US7902332B2 (en) | 2006-11-30 | 2011-03-08 | General Electric Company | Fluorine-labeled compounds |
EP2099496A2 (en) | 2006-12-08 | 2009-09-16 | Massachusetts Institute of Technology | Delivery of nanoparticles and/or agents to cells |
US8062215B2 (en) | 2007-04-13 | 2011-11-22 | Ethicon Endo-Surgery, Inc. | Fluorescent nanoparticle scope |
EP1995327A1 (en) | 2007-05-21 | 2008-11-26 | Humboldt Universität zu Berlin | Probe for detecting a particular nucleic acid sequence |
WO2009029870A2 (en) | 2007-08-31 | 2009-03-05 | Hybrid Silica Technologies, Inc. | Peg-coated core-shell silica nanoparticles and methods of manufacture and use |
DE102007052517A1 (de) | 2007-10-29 | 2009-04-30 | Autoimmun Diagnostika Gmbh | ELISPOT-Verfahren mit zwei Filtersystemen |
US8968699B2 (en) | 2007-11-15 | 2015-03-03 | The Regents Of The University Of California | Switchable nano-vehicle delivery systems, and methods for making and using them |
WO2009085218A1 (en) | 2007-12-21 | 2009-07-09 | President And Fellows Of Harvard College | Sub-diffraction limit image resolution in three dimensions |
WO2010091294A2 (en) | 2009-02-05 | 2010-08-12 | The Regents Of The University Of California | New targeted antimicrobial moieties |
JP5717720B2 (ja) | 2009-04-15 | 2015-05-13 | コーネル ユニバーシティCornell University | シリカの高密度化で改良された蛍光シリカナノ粒子 |
WO2011005380A2 (en) | 2009-06-12 | 2011-01-13 | Stc. Unm | Arg-gly-asp-conjugated alpha-melanocyte stimulating hormone hybrid peptide for use in diagnosing and treating melanoma, including metastatic melanoma and methods related to same |
US20230158180A1 (en) | 2009-07-02 | 2023-05-25 | Sloan-Kettering Institute For Cancer Research | Multimodal silica-based nanoparticles |
EP2512522A4 (en) | 2009-12-16 | 2013-09-25 | Brigham & Womens Hospital | PARTICULARS FOR THE DELIVERY OF SEVERAL ACTIVE SUBSTANCES |
US9238069B2 (en) * | 2009-12-16 | 2016-01-19 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Method of sensitizing cancer cells to the cytotoxic effects of death receptor ligands in cancer treatment |
PE20130342A1 (es) | 2010-04-15 | 2013-04-20 | Spirogen Sarl | Pirrolobenzodiacepinas y conjugados de las mismas |
GB201121288D0 (en) | 2011-12-12 | 2012-01-25 | Univ Muenster Wilhelms | Functionalised silicon nanoparticles |
US9006987B2 (en) | 2012-05-07 | 2015-04-14 | Lighting Science Group, Inc. | Wall-mountable luminaire and associated systems and methods |
EP2863952B1 (en) | 2012-06-22 | 2018-09-12 | Cornell University | Mesoporous oxide nanoparticles and methods of making and using same |
US9695133B2 (en) | 2012-07-13 | 2017-07-04 | The Trustees Of Columbia University In The City Of New York | Quinazolinone-based oncogenic-RAS-selective lethal compounds and their use |
CN112587658A (zh) | 2012-07-18 | 2021-04-02 | 博笛生物科技有限公司 | 癌症的靶向免疫治疗 |
ES2709886T3 (es) | 2013-02-20 | 2019-04-22 | Univ Cornell | Nanopartículas fluorescentes multicapa y procedimientos de fabricación y uso de las mismas |
BR112015020782A2 (pt) | 2013-03-15 | 2017-10-10 | Univ Cornell | nanopartículas à base de sílica multimodal |
AU2014373656B2 (en) | 2013-12-31 | 2019-12-05 | Cornell University | Systems, methods, and apparatus for multichannel imaging of fluorescent sources in real time |
CN106659797B (zh) | 2014-05-29 | 2021-04-27 | 纪念斯隆-凯特琳癌症中心 | 纳米粒子药物结合物 |
US10799604B2 (en) | 2014-07-25 | 2020-10-13 | Northeastern University | Biopolymer-nanoparticle composite implant for tumor cell tracking |
EP3029032A1 (en) | 2014-12-05 | 2016-06-08 | Centre National de la Recherche Scientifique (CNRS) | Bifunctional do2pa derivatives, chelates with metallic cations and use thereof |
CA2970719C (en) | 2014-12-15 | 2023-08-01 | Memorial Sloan Kettering Cancer Center | Cyclic peptides with enhanced nerve-binding selectivity, nanoparticles bound with said cyclic peptides, and use of same for real-time in vivo nerve tissue imaging |
EP3280454A1 (en) | 2015-04-07 | 2018-02-14 | Memorial Sloan Kettering Cancer Center | Nanoparticle immunoconjugates |
AU2016257431B2 (en) | 2015-05-04 | 2021-08-05 | Cornell University | Ultrasmall nanoparticles and methods of making and using same |
AU2016271040A1 (en) | 2015-05-29 | 2017-11-23 | Cornell University | Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis |
EP3347025A4 (en) | 2015-09-11 | 2019-04-24 | Memorial Sloan-Kettering Cancer Center | METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER |
JP2020500863A (ja) | 2016-11-30 | 2020-01-16 | メモリアル スローン ケタリング キャンサー センター | 阻害剤官能化超小型ナノ粒子およびその方法 |
US20200155710A1 (en) | 2017-04-10 | 2020-05-21 | Cornell University | Sulfur- or heavy atom-containing nanoparticles, methods of making same, and uses thereof |
EP3624777A4 (en) | 2017-05-19 | 2021-03-10 | Cornell University | FUNCTIONALIZED NANOPARTICLE AND METHOD FOR MANUFACTURING AND USING THEREOF |
US20200138829A1 (en) | 2017-05-24 | 2020-05-07 | Ferro Therapeutics, Inc. | Methods of cancer treatment |
WO2018217528A1 (en) | 2017-05-25 | 2018-11-29 | Memorial Sloan Kettering Cancer Center | Ultrasmall nanoparticles labeled with zirconium-89 and methods thereof |
US20210145985A1 (en) | 2017-06-23 | 2021-05-20 | Memorial Sloan Kettering Cancer Center | Method of imaging in vivo tissues using nanoparticles comprising a reference dye and a sensor dye |
US20200383943A1 (en) | 2017-12-04 | 2020-12-10 | Memorial Sloan Kettering Cancer Center | Methods of cancer treatment via regulated ferroptosis |
-
2016
- 2016-05-26 AU AU2016271040A patent/AU2016271040A1/en not_active Abandoned
- 2016-05-26 WO PCT/US2016/034351 patent/WO2016196201A1/en active Application Filing
- 2016-05-26 EP EP16730103.5A patent/EP3302568B1/en active Active
- 2016-05-26 KR KR1020177037129A patent/KR20180012299A/ko not_active Application Discontinuation
- 2016-05-26 BR BR112017024328A patent/BR112017024328A2/pt not_active Application Discontinuation
- 2016-05-26 CN CN201680035303.4A patent/CN108377643B/zh active Active
- 2016-05-26 US US15/573,855 patent/US10736972B2/en active Active
- 2016-05-26 JP JP2017560717A patent/JP6974178B2/ja active Active
- 2016-05-26 CA CA2985126A patent/CA2985126A1/en not_active Abandoned
- 2016-05-26 CN CN202111011162.1A patent/CN113559279A/zh active Pending
-
2018
- 2018-10-05 HK HK18112736.4A patent/HK1253536A1/zh unknown
-
2020
- 2020-06-16 US US16/902,577 patent/US11246946B2/en active Active
-
2021
- 2021-11-04 JP JP2021180243A patent/JP7263485B2/ja active Active
- 2021-12-30 US US17/566,015 patent/US11931425B2/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130039848A1 (en) * | 2009-07-02 | 2013-02-14 | Cornell University | Fluorescent silica-based nanoparticles |
Non-Patent Citations (3)
Title |
---|
CANCER RES, vol. 69, no. 16, JPN6020015451, 2009, pages 6515 - 6521, ISSN: 0004475599 * |
EMMA LACHAIER: "SORAFENIB INDUCES FERROPTOSIS IN HUMAN CANCER CELL LINES ORIGINATING FROM DIFFERENT SOLID TUMORS", ANTICANCER RESEARCH, vol. 34, JPN5018003365, November 2014 (2014-11-01), pages 6417 - 6422, ISSN: 0004475597 * |
SCOTT J DIXON: "FERROPTOSIS: AN IRON-DEPENDENT FORM OF NONAPOPTOTIC CELL DEATH", CELL, vol. VOL:149, NR:5, JPN5018003366, May 2012 (2012-05-01), pages 1060 - 1072, ISSN: 0004475598 * |
Also Published As
Publication number | Publication date |
---|---|
CN108377643B (zh) | 2021-09-21 |
CN108377643A (zh) | 2018-08-07 |
EP3302568B1 (en) | 2023-12-06 |
JP2022023210A (ja) | 2022-02-07 |
US10736972B2 (en) | 2020-08-11 |
US20180169264A1 (en) | 2018-06-21 |
WO2016196201A1 (en) | 2016-12-08 |
AU2016271040A1 (en) | 2017-11-23 |
JP7263485B2 (ja) | 2023-04-24 |
US11246946B2 (en) | 2022-02-15 |
US20200316219A1 (en) | 2020-10-08 |
EP3302568A1 (en) | 2018-04-11 |
CN113559279A (zh) | 2021-10-29 |
JP6974178B2 (ja) | 2021-12-01 |
CA2985126A1 (en) | 2016-12-08 |
KR20180012299A (ko) | 2018-02-05 |
BR112017024328A2 (pt) | 2018-07-24 |
US11931425B2 (en) | 2024-03-19 |
HK1253536A1 (zh) | 2019-06-21 |
US20220118106A1 (en) | 2022-04-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7263485B2 (ja) | フェロトーシスを介して栄養欠乏がん細胞の細胞死を誘導するための極小ナノ粒子を使用する処置方法 | |
Ahmad et al. | Precision cancer nanotherapy: evolving role of multifunctional nanoparticles for cancer active targeting | |
da Silva Santos et al. | EGFR targeting for cancer therapy: Pharmacology and immunoconjugates with drugs and nanoparticles | |
Sun et al. | Synergistic triple-combination therapy with hyaluronic acid-shelled PPy/CPT nanoparticles results in tumor regression and prevents tumor recurrence and metastasis in 4T1 breast cancer | |
Fan et al. | Near infrared fluorescent peptide nanoparticles for enhancing esophageal cancer therapeutic efficacy | |
Wang et al. | Quantum-dot-based theranostic micelles conjugated with an anti-EGFR nanobody for triple-negative breast cancer therapy | |
Wang et al. | Epirubicin-adsorbed nanodiamonds kill chemoresistant hepatic cancer stem cells | |
Wang et al. | Nanoparticulate delivery system targeted to tumor neovasculature for combined anticancer and antiangiogenesis therapy | |
Anhorn et al. | Specific targeting of HER2 overexpressing breast cancer cells with doxorubicin-loaded trastuzumab-modified human serum albumin nanoparticles | |
JP6373281B2 (ja) | ナノ粒子送達組成物 | |
JP7455510B2 (ja) | 悪性脳腫瘍における標的化粒子の浸透、分布および応答のための組成物及び方法 | |
Sulthana et al. | Combination therapy of NSCLC using Hsp90 inhibitor and doxorubicin carrying functional nanoceria | |
Cai et al. | Cellular uptake and internalization of hyaluronan-based doxorubicin and cisplatin conjugates | |
Wu et al. | Peptide-functionalized nanoinhibitor restrains brain tumor growth by abrogating mesenchymal-epithelial transition factor (MET) signaling | |
Kumar et al. | Targeting macrophages: a novel avenue for cancer drug discovery | |
Zhao et al. | A hindsight reflection on the clinical studies of poly (l‐glutamic acid)‐paclitaxel | |
Shrestha et al. | Targeting Cancer Stem Cells: Therapeutic and diagnostic strategies by the virtue of nanoparticles | |
Ruoslahti | Access granted: iRGD helps silicasome-encased drugs breach the tumor barrier | |
Choudhury et al. | Recent progress of targeted nanocarriers in diagnostic, therapeutic, and theranostic applications in colorectal cancer | |
Valsalakumari et al. | Preclinical Efficacy of Cabazitaxel Loaded Poly (2-alkyl cyanoacrylate) Nanoparticle Variants | |
Gholami et al. | A comprehensive perspective of trastuzumab-based delivery systems for breast cancer treatment | |
Sree | Nano-Particulate Drug Carriers for Effective Targeting and Drug Delivery to Bladder Tumors | |
Manjunatha | Nanoparticles Mediated Targeted Drug Delivery System of Some Antineoplastic Agents for the Treatment of Breast Cancer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180123 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190509 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190509 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200513 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200806 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200925 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201111 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210330 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210624 |
|
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: 20211004 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20211104 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6974178 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |