JP2017524002A - インビトロおよびインビボにおける標的の光制御除去 - Google Patents
インビトロおよびインビボにおける標的の光制御除去 Download PDFInfo
- Publication number
- JP2017524002A JP2017524002A JP2017506895A JP2017506895A JP2017524002A JP 2017524002 A JP2017524002 A JP 2017524002A JP 2017506895 A JP2017506895 A JP 2017506895A JP 2017506895 A JP2017506895 A JP 2017506895A JP 2017524002 A JP2017524002 A JP 2017524002A
- Authority
- JP
- Japan
- Prior art keywords
- target
- molecule
- conjugate
- cells
- sample
- 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
- 238000001727 in vivo Methods 0.000 title abstract description 58
- 238000000338 in vitro Methods 0.000 title abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 228
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 55
- 235000013305 food Nutrition 0.000 claims abstract description 17
- 230000007613 environmental effect Effects 0.000 claims abstract description 16
- 210000004027 cell Anatomy 0.000 claims description 343
- 206010028980 Neoplasm Diseases 0.000 claims description 149
- 108090000623 proteins and genes Proteins 0.000 claims description 141
- 102000004169 proteins and genes Human genes 0.000 claims description 138
- 150000007523 nucleic acids Chemical class 0.000 claims description 132
- 102000039446 nucleic acids Human genes 0.000 claims description 131
- 108020004707 nucleic acids Proteins 0.000 claims description 131
- 230000009870 specific binding Effects 0.000 claims description 94
- 239000011230 binding agent Substances 0.000 claims description 91
- 239000002523 lectin Substances 0.000 claims description 48
- 102000004856 Lectins Human genes 0.000 claims description 45
- 108090001090 Lectins Proteins 0.000 claims description 45
- 201000011510 cancer Diseases 0.000 claims description 44
- 230000027455 binding Effects 0.000 claims description 43
- 238000009739 binding Methods 0.000 claims description 43
- 244000052769 pathogen Species 0.000 claims description 43
- 210000004369 blood Anatomy 0.000 claims description 36
- 239000008280 blood Substances 0.000 claims description 36
- 229910052751 metal Inorganic materials 0.000 claims description 34
- 239000002184 metal Substances 0.000 claims description 33
- 150000001720 carbohydrates Chemical class 0.000 claims description 25
- -1 antibiotic Substances 0.000 claims description 24
- 230000001717 pathogenic effect Effects 0.000 claims description 19
- 210000000130 stem cell Anatomy 0.000 claims description 19
- 210000004185 liver Anatomy 0.000 claims description 18
- 239000012634 fragment Substances 0.000 claims description 15
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 claims description 13
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims description 13
- 230000002776 aggregation Effects 0.000 claims description 13
- 238000004220 aggregation Methods 0.000 claims description 13
- 239000002246 antineoplastic agent Substances 0.000 claims description 13
- 230000001678 irradiating effect Effects 0.000 claims description 13
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims description 11
- 229940088597 hormone Drugs 0.000 claims description 11
- 239000005556 hormone Substances 0.000 claims description 11
- 210000002865 immune cell Anatomy 0.000 claims description 11
- 210000003491 skin Anatomy 0.000 claims description 11
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 10
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 10
- 229940127089 cytotoxic agent Drugs 0.000 claims description 10
- 229940127121 immunoconjugate Drugs 0.000 claims description 9
- 239000008188 pellet Substances 0.000 claims description 9
- 239000003237 recreational drug Substances 0.000 claims description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 8
- 210000004881 tumor cell Anatomy 0.000 claims description 8
- 206010009944 Colon cancer Diseases 0.000 claims description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- 239000006228 supernatant Substances 0.000 claims description 6
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 238000000855 fermentation Methods 0.000 claims description 5
- 230000004151 fermentation Effects 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 239000002831 pharmacologic agent Substances 0.000 claims description 5
- 150000003431 steroids Chemical class 0.000 claims description 5
- 239000000935 antidepressant agent Substances 0.000 claims description 4
- 229940005513 antidepressants Drugs 0.000 claims description 4
- 239000003124 biologic agent Substances 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 210000000496 pancreas Anatomy 0.000 claims description 4
- 230000001850 reproductive effect Effects 0.000 claims description 4
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
- 239000002220 antihypertensive agent Substances 0.000 claims description 3
- 229940030600 antihypertensive agent Drugs 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 210000003289 regulatory T cell Anatomy 0.000 claims description 3
- 206010046766 uterine cancer Diseases 0.000 claims description 3
- 206010005949 Bone cancer Diseases 0.000 claims description 2
- 208000018084 Bone neoplasm Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 210000004291 uterus Anatomy 0.000 claims description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 claims 1
- 230000000202 analgesic effect Effects 0.000 claims 1
- 230000001430 anti-depressive effect Effects 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 70
- 229940079593 drug Drugs 0.000 abstract description 62
- 150000002433 hydrophilic molecules Chemical class 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract 1
- 239000000562 conjugate Substances 0.000 description 213
- 239000000523 sample Substances 0.000 description 147
- 239000003795 chemical substances by application Substances 0.000 description 72
- 230000000694 effects Effects 0.000 description 44
- 239000000427 antigen Substances 0.000 description 43
- 108091007433 antigens Proteins 0.000 description 42
- 102000036639 antigens Human genes 0.000 description 42
- 239000002773 nucleotide Substances 0.000 description 39
- 125000003729 nucleotide group Chemical group 0.000 description 39
- 238000005415 bioluminescence Methods 0.000 description 38
- 230000029918 bioluminescence Effects 0.000 description 38
- 241000282414 Homo sapiens Species 0.000 description 35
- 239000003053 toxin Substances 0.000 description 33
- 231100000765 toxin Toxicity 0.000 description 33
- 108700012359 toxins Proteins 0.000 description 33
- 239000000203 mixture Substances 0.000 description 30
- 238000011282 treatment Methods 0.000 description 29
- 108091023037 Aptamer Proteins 0.000 description 28
- 108091027757 Deoxyribozyme Proteins 0.000 description 27
- 241000700605 Viruses Species 0.000 description 27
- 230000003247 decreasing effect Effects 0.000 description 27
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 26
- 108020004414 DNA Proteins 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 25
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 24
- 108060001084 Luciferase Proteins 0.000 description 23
- 239000005089 Luciferase Substances 0.000 description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
- 210000000056 organ Anatomy 0.000 description 22
- 108060003951 Immunoglobulin Proteins 0.000 description 21
- 235000014633 carbohydrates Nutrition 0.000 description 21
- 231100000673 dose–response relationship Toxicity 0.000 description 21
- 102000018358 immunoglobulin Human genes 0.000 description 21
- 230000000295 complement effect Effects 0.000 description 20
- 210000004215 spore Anatomy 0.000 description 20
- 238000011002 quantification Methods 0.000 description 19
- 239000000243 solution Substances 0.000 description 18
- 150000002739 metals Chemical class 0.000 description 17
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 16
- 102100040069 Aldehyde dehydrogenase 1A1 Human genes 0.000 description 15
- 102000001301 EGF receptor Human genes 0.000 description 15
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 15
- 238000004113 cell culture Methods 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- 230000008030 elimination Effects 0.000 description 15
- 238000003379 elimination reaction Methods 0.000 description 15
- 201000010225 mixed cell type cancer Diseases 0.000 description 15
- 208000029638 mixed neoplasm Diseases 0.000 description 15
- 229910052760 oxygen Inorganic materials 0.000 description 15
- 210000003995 blood forming stem cell Anatomy 0.000 description 14
- 230000006378 damage Effects 0.000 description 14
- 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 14
- 239000000463 material Substances 0.000 description 14
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 14
- 239000002953 phosphate buffered saline Substances 0.000 description 14
- 241000894006 Bacteria Species 0.000 description 13
- 108060006698 EGF receptor Proteins 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 230000002354 daily effect Effects 0.000 description 13
- 239000001301 oxygen Substances 0.000 description 13
- 229960000575 trastuzumab Drugs 0.000 description 13
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 12
- 244000005700 microbiome Species 0.000 description 12
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 12
- 239000002435 venom Substances 0.000 description 12
- 210000001048 venom Anatomy 0.000 description 12
- 231100000611 venom Toxicity 0.000 description 12
- 102100032912 CD44 antigen Human genes 0.000 description 11
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 11
- 150000001413 amino acids Chemical class 0.000 description 11
- 238000003776 cleavage reaction Methods 0.000 description 11
- 229960001972 panitumumab Drugs 0.000 description 11
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 11
- 230000007017 scission Effects 0.000 description 11
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 10
- 208000009956 adenocarcinoma Diseases 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 10
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 102000004127 Cytokines Human genes 0.000 description 9
- 108090000695 Cytokines Proteins 0.000 description 9
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 210000001185 bone marrow Anatomy 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 239000012530 fluid Substances 0.000 description 9
- 238000000799 fluorescence microscopy Methods 0.000 description 9
- 229910001385 heavy metal Inorganic materials 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 208000032839 leukemia Diseases 0.000 description 9
- 229910021645 metal ion Inorganic materials 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000010186 staining Methods 0.000 description 9
- 229940124597 therapeutic agent Drugs 0.000 description 9
- 208000023275 Autoimmune disease Diseases 0.000 description 8
- 241000233866 Fungi Species 0.000 description 8
- 101000890570 Homo sapiens Aldehyde dehydrogenase 1A1 Proteins 0.000 description 8
- 239000003242 anti bacterial agent Substances 0.000 description 8
- 229940088710 antibiotic agent Drugs 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 239000000975 dye Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 230000017074 necrotic cell death Effects 0.000 description 8
- 210000000952 spleen Anatomy 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 7
- 101710133479 Aldehyde dehydrogenase 1A1 Proteins 0.000 description 7
- 241000193738 Bacillus anthracis Species 0.000 description 7
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 7
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 7
- 102000018697 Membrane Proteins Human genes 0.000 description 7
- 108010052285 Membrane Proteins Proteins 0.000 description 7
- 206010039491 Sarcoma Diseases 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 238000003384 imaging method Methods 0.000 description 7
- 230000002147 killing effect Effects 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 201000001441 melanoma Diseases 0.000 description 7
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 108091092562 ribozyme Proteins 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000012605 2D cell culture Methods 0.000 description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 6
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 6
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 6
- 102100022595 Broad substrate specificity ATP-binding cassette transporter ABCG2 Human genes 0.000 description 6
- 102100024210 CD166 antigen Human genes 0.000 description 6
- 108090000994 Catalytic RNA Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 101100058548 Felis catus BMI1 gene Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 108010090306 Member 2 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 6
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 6
- 102100038358 Prostate-specific antigen Human genes 0.000 description 6
- 210000001015 abdomen Anatomy 0.000 description 6
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 6
- 210000003719 b-lymphocyte Anatomy 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 230000005284 excitation Effects 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 208000002672 hepatitis B Diseases 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 206010041823 squamous cell carcinoma Diseases 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 5
- 102000053642 Catalytic RNA Human genes 0.000 description 5
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 5
- 206010025323 Lymphomas Diseases 0.000 description 5
- 102100023123 Mucin-16 Human genes 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 238000002617 apheresis Methods 0.000 description 5
- 239000012472 biological sample Substances 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 229960003920 cocaine Drugs 0.000 description 5
- 230000000254 damaging effect Effects 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- 239000003504 photosensitizing agent Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 231100000331 toxic Toxicity 0.000 description 5
- 230000002588 toxic effect Effects 0.000 description 5
- 102100040410 Alpha-methylacyl-CoA racemase Human genes 0.000 description 4
- 108010044434 Alpha-methylacyl-CoA racemase Proteins 0.000 description 4
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 4
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 4
- 102000000844 Cell Surface Receptors Human genes 0.000 description 4
- 108010001857 Cell Surface Receptors Proteins 0.000 description 4
- 102100037241 Endoglin Human genes 0.000 description 4
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 4
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 4
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 description 4
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 4
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 4
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 4
- 102000003886 Glycoproteins Human genes 0.000 description 4
- 108090000288 Glycoproteins Proteins 0.000 description 4
- 208000031886 HIV Infections Diseases 0.000 description 4
- 208000005331 Hepatitis D Diseases 0.000 description 4
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 4
- 101000920667 Homo sapiens Epithelial cell adhesion molecule Proteins 0.000 description 4
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 4
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 102000029749 Microtubule Human genes 0.000 description 4
- 108091022875 Microtubule Proteins 0.000 description 4
- 108010046016 Peanut Agglutinin Proteins 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 229940121991 Serotonin and norepinephrine reuptake inhibitor Drugs 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 4
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 230000007815 allergy Effects 0.000 description 4
- 229940034982 antineoplastic agent Drugs 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 230000002146 bilateral effect Effects 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 229960005395 cetuximab Drugs 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 241001493065 dsRNA viruses Species 0.000 description 4
- 238000001962 electrophoresis Methods 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 229940028334 follicle stimulating hormone Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 4
- 229910052737 gold Inorganic materials 0.000 description 4
- 239000010931 gold Substances 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000009931 harmful effect Effects 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 210000002751 lymph Anatomy 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 210000004688 microtubule Anatomy 0.000 description 4
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 244000045947 parasite Species 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000000955 prescription drug Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 4
- 230000003252 repetitive effect Effects 0.000 description 4
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 4
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 4
- 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000004611 spectroscopical analysis Methods 0.000 description 4
- 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 4
- 238000002054 transplantation Methods 0.000 description 4
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 108010075348 Activated-Leukocyte Cell Adhesion Molecule Proteins 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 3
- 108010065524 CD52 Antigen Proteins 0.000 description 3
- 229940045513 CTLA4 antagonist Drugs 0.000 description 3
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 3
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 108010062580 Concanavalin A Proteins 0.000 description 3
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 3
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 3
- 108091008102 DNA aptamers Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
- 241000196324 Embryophyta Species 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 3
- 101710154606 Hemagglutinin Proteins 0.000 description 3
- 241000709721 Hepatovirus A Species 0.000 description 3
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 3
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 3
- 101001063456 Homo sapiens Leucine-rich repeat-containing G-protein coupled receptor 5 Proteins 0.000 description 3
- 101001008874 Homo sapiens Mast/stem cell growth factor receptor Kit Proteins 0.000 description 3
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 3
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 3
- 101150017554 LGR5 gene Proteins 0.000 description 3
- 102100031036 Leucine-rich repeat-containing G-protein coupled receptor 5 Human genes 0.000 description 3
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 3
- 241000186781 Listeria Species 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 3
- 108050008953 Melanoma-associated antigen Proteins 0.000 description 3
- 102000000440 Melanoma-associated antigen Human genes 0.000 description 3
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 3
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 3
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 3
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 3
- SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 description 3
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 3
- 206010028851 Necrosis Diseases 0.000 description 3
- 108010088225 Nestin Proteins 0.000 description 3
- 102000008730 Nestin Human genes 0.000 description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 3
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 3
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- 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 3
- 101710176177 Protein A56 Proteins 0.000 description 3
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 3
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 3
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 3
- 244000151637 Sambucus canadensis Species 0.000 description 3
- 235000018735 Sambucus canadensis Nutrition 0.000 description 3
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 3
- 208000024313 Testicular Neoplasms Diseases 0.000 description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 3
- 240000002895 Vicia hirsuta Species 0.000 description 3
- 101001074046 Xenopus laevis Zinc finger protein GLI1 Proteins 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003570 air Substances 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 3
- 235000007123 blue elder Nutrition 0.000 description 3
- 229910052793 cadmium Inorganic materials 0.000 description 3
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 229960002069 diamorphine Drugs 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- 229960004242 dronabinol Drugs 0.000 description 3
- 235000013399 edible fruits Nutrition 0.000 description 3
- 235000007124 elderberry Nutrition 0.000 description 3
- 231100000655 enterotoxin Toxicity 0.000 description 3
- 229930013356 epothilone Natural products 0.000 description 3
- 235000008995 european elder Nutrition 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000002073 fluorescence micrograph Methods 0.000 description 3
- 229930182830 galactose Natural products 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000000185 hemagglutinin Substances 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- CBCIHIVRDWLAME-UHFFFAOYSA-N hexanitrodiphenylamine Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1NC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O CBCIHIVRDWLAME-UHFFFAOYSA-N 0.000 description 3
- 102000045108 human EGFR Human genes 0.000 description 3
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 3
- 238000010191 image analysis Methods 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 108010034897 lentil lectin Proteins 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 235000013372 meat Nutrition 0.000 description 3
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 3
- 229910052753 mercury Inorganic materials 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 229950006780 n-acetylglucosamine Drugs 0.000 description 3
- 210000005055 nestin Anatomy 0.000 description 3
- 231100000618 neurotoxin Toxicity 0.000 description 3
- 239000002581 neurotoxin Substances 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 229960002085 oxycodone Drugs 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 229960005489 paracetamol Drugs 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 229960003387 progesterone Drugs 0.000 description 3
- 239000000186 progesterone Substances 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 3
- 108010076805 snowdrop lectin Proteins 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 230000003075 superhydrophobic effect Effects 0.000 description 3
- 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 3
- 201000003120 testicular cancer Diseases 0.000 description 3
- 229940126585 therapeutic drug Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000017423 tissue regeneration Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000005945 translocation Effects 0.000 description 3
- 235000013311 vegetables Nutrition 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- 238000012604 3D cell culture Methods 0.000 description 2
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 2
- 102100021501 ATP-binding cassette sub-family B member 5 Human genes 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 101710186708 Agglutinin Proteins 0.000 description 2
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 2
- 102100022749 Aminopeptidase N Human genes 0.000 description 2
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 2
- 241000239290 Araneae Species 0.000 description 2
- 241000242587 Aurelia Species 0.000 description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 102100026094 C-type lectin domain family 12 member A Human genes 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 102100027207 CD27 antigen Human genes 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 241000223935 Cryptosporidium Species 0.000 description 2
- 108010058546 Cyclin D1 Proteins 0.000 description 2
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 2
- 239000012625 DNA intercalator Substances 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 241000450599 DNA viruses Species 0.000 description 2
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108010036395 Endoglin Proteins 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 241000714165 Feline leukemia virus Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 102100020997 Fractalkine Human genes 0.000 description 2
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 2
- 102100021337 Gap junction alpha-1 protein Human genes 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 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 2
- 102000017011 Glycated Hemoglobin A Human genes 0.000 description 2
- 102100035716 Glycophorin-A Human genes 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 2
- 101000677872 Homo sapiens ATP-binding cassette sub-family B member 5 Proteins 0.000 description 2
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 2
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 2
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 2
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 2
- 101001094647 Homo sapiens Serum paraoxonase/arylesterase 1 Proteins 0.000 description 2
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 2
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 2
- 101710146024 Horcolin Proteins 0.000 description 2
- 241000546188 Hypericum Species 0.000 description 2
- 235000017309 Hypericum perforatum Nutrition 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 2
- 102100032816 Integrin alpha-6 Human genes 0.000 description 2
- 108010041100 Integrin alpha6 Proteins 0.000 description 2
- 102000000426 Integrin alpha6 Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 101710189395 Lectin Proteins 0.000 description 2
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 2
- 102100022119 Lipoprotein lipase Human genes 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 101710179758 Mannose-specific lectin Proteins 0.000 description 2
- 101710150763 Mannose-specific lectin 1 Proteins 0.000 description 2
- 101710150745 Mannose-specific lectin 2 Proteins 0.000 description 2
- 208000000172 Medulloblastoma Diseases 0.000 description 2
- 206010027406 Mesothelioma Diseases 0.000 description 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 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
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 description 2
- 241000244206 Nematoda Species 0.000 description 2
- 101710138657 Neurotoxin Proteins 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 2
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 2
- ZRWPUFFVAOMMNM-UHFFFAOYSA-N Patulin Chemical compound OC1OCC=C2OC(=O)C=C12 ZRWPUFFVAOMMNM-UHFFFAOYSA-N 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 241000009328 Perro Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 description 2
- 102000007987 Proto-Oncogene Proteins c-maf Human genes 0.000 description 2
- 108010089507 Proto-Oncogene Proteins c-maf Proteins 0.000 description 2
- 102100034026 RNA-binding protein Musashi homolog 1 Human genes 0.000 description 2
- 101710129077 RNA-binding protein Musashi homolog 1 Proteins 0.000 description 2
- 238000001069 Raman spectroscopy Methods 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 241000725643 Respiratory syncytial virus Species 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 2
- 241000239226 Scorpiones Species 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 241000270295 Serpentes Species 0.000 description 2
- 102100035476 Serum paraoxonase/arylesterase 1 Human genes 0.000 description 2
- 108010079723 Shiga Toxin Proteins 0.000 description 2
- 102100038081 Signal transducer CD24 Human genes 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 102100035721 Syndecan-1 Human genes 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 2
- 101150052863 THY1 gene Proteins 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 206010057644 Testis cancer Diseases 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 description 2
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 2
- 102000011923 Thyrotropin Human genes 0.000 description 2
- 108010061174 Thyrotropin Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 229910052770 Uranium Inorganic materials 0.000 description 2
- 101710099833 Venom protein Proteins 0.000 description 2
- 241000710886 West Nile virus Species 0.000 description 2
- 208000008383 Wilms tumor Diseases 0.000 description 2
- 102100022748 Wilms tumor protein Human genes 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 239000000910 agglutinin Substances 0.000 description 2
- 230000004931 aggregating effect Effects 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- 229940005529 antipsychotics Drugs 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229940065181 bacillus anthracis Drugs 0.000 description 2
- 239000003855 balanced salt solution Substances 0.000 description 2
- 229960004669 basiliximab Drugs 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 229960001736 buprenorphine Drugs 0.000 description 2
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 108091008400 carbohydrate binding proteins Proteins 0.000 description 2
- 102000023852 carbohydrate binding proteins Human genes 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 208000025997 central nervous system neoplasm Diseases 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 229960004126 codeine Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 229940111134 coxibs Drugs 0.000 description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 229960002806 daclizumab Drugs 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 230000000779 depleting effect Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 238000007905 drug manufacturing Methods 0.000 description 2
- 239000003596 drug target Substances 0.000 description 2
- 239000002532 enzyme inhibitor Substances 0.000 description 2
- 201000005616 epidermal appendage tumor Diseases 0.000 description 2
- 150000003883 epothilone derivatives Chemical class 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 201000009277 hairy cell leukemia Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 208000037797 influenza A Diseases 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 210000004324 lymphatic system Anatomy 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229960001252 methamphetamine Drugs 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 2
- 229960000282 metronidazole Drugs 0.000 description 2
- 229940099246 mevacor Drugs 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000009149 molecular binding Effects 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 229910052755 nonmetal Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 239000003865 nucleic acid synthesis inhibitor Substances 0.000 description 2
- 229940124636 opioid drug Drugs 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 2
- 201000010198 papillary carcinoma Diseases 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 2
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 2
- 239000001007 phthalocyanine dye Substances 0.000 description 2
- 101150032777 pit gene Proteins 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 229940089484 pravachol Drugs 0.000 description 2
- TUZYXOIXSAXUGO-PZAWKZKUSA-M pravastatin(1-) Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC([O-])=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-M 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 229940035613 prozac Drugs 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
- 239000003998 snake venom Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 206010042863 synovial sarcoma Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 239000003451 thiazide diuretic agent Substances 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 239000000439 tumor marker Substances 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 229960005080 warfarin Drugs 0.000 description 2
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 229940072168 zocor Drugs 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- DHPRQBPJLMKORJ-XRNKAMNCSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O DHPRQBPJLMKORJ-XRNKAMNCSA-N 0.000 description 1
- MBMQEIFVQACCCH-XVNBXDOJSA-N (S,E)-Zearalenone Chemical compound O=C1OC(C)CCCC(=O)CCC\C=C\C2=CC(O)=CC(O)=C21 MBMQEIFVQACCCH-XVNBXDOJSA-N 0.000 description 1
- SGNXVBOIDPPRJJ-PSASIEDQSA-N 1-[(1r,6r)-9-azabicyclo[4.2.1]non-4-en-5-yl]ethanone Chemical compound CC(=O)C1=CCC[C@@H]2CC[C@H]1N2 SGNXVBOIDPPRJJ-PSASIEDQSA-N 0.000 description 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 1
- VAOYPHGXHKUTHC-KRWDZBQOSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-[(2s)-2-[bis(carboxymethyl)amino]-3-(4-isothiocyanatophenyl)propyl]amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)C[C@@H](N(CC(O)=O)CC(O)=O)CC1=CC=C(N=C=S)C=C1 VAOYPHGXHKUTHC-KRWDZBQOSA-N 0.000 description 1
- QZDDFQLIQRYMBV-UHFFFAOYSA-N 2-[3-nitro-2-(2-nitrophenyl)-4-oxochromen-8-yl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(C=2[N+]([O-])=O)=O)=C1OC=2C1=CC=CC=C1[N+]([O-])=O QZDDFQLIQRYMBV-UHFFFAOYSA-N 0.000 description 1
- 101710111653 2-methylisocitrate lyase Proteins 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
- XAEPFBXVLMACNN-UHFFFAOYSA-N 3-[10,15,20-tris(3-hydroxyphenyl)-21,24-dihydroporphyrin-5-yl]phenol Chemical compound OC1=CC=CC(C=2C=3C=CC(N=3)=C(C=3C=C(O)C=CC=3)C3=CC=C(N3)C(C=3C=C(O)C=CC=3)=C3C=CC(N3)=C(C=3C=C(O)C=CC=3)C=3C=CC=2N=3)=C1 XAEPFBXVLMACNN-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical group 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
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 1
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-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
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-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
- 241000224422 Acanthamoeba Species 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 206010001197 Adenocarcinoma of the cervix Diseases 0.000 description 1
- 208000034246 Adenocarcinoma of the cervix uteri Diseases 0.000 description 1
- 208000036764 Adenocarcinoma of the esophagus Diseases 0.000 description 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
- 229930195730 Aflatoxin Natural products 0.000 description 1
- XWIYFDMXXLINPU-UHFFFAOYSA-N Aflatoxin G Chemical compound O=C1OCCC2=C1C(=O)OC1=C2C(OC)=CC2=C1C1C=COC1O2 XWIYFDMXXLINPU-UHFFFAOYSA-N 0.000 description 1
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 description 1
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- SGNXVBOIDPPRJJ-UHFFFAOYSA-N Anatoxin a Natural products CC(=O)C1=CCCC2CCC1N2 SGNXVBOIDPPRJJ-UHFFFAOYSA-N 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000004300 Atrophic Gastritis Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 241000713842 Avian sarcoma virus Species 0.000 description 1
- 102100035526 B melanoma antigen 1 Human genes 0.000 description 1
- 102100035565 B melanoma antigen 2 Human genes 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 1
- 108091012583 BCL2 Proteins 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241001235574 Balantidium Species 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 206010004585 Bile duct adenocarcinoma Diseases 0.000 description 1
- 241000335423 Blastomyces Species 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108030001720 Bontoxilysin Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 208000006274 Brain Stem Neoplasms Diseases 0.000 description 1
- 102100025401 Breast cancer type 1 susceptibility protein Human genes 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- 101710188619 C-type lectin domain family 12 member A Proteins 0.000 description 1
- 108010008629 CA-125 Antigen Proteins 0.000 description 1
- UJKPHYRXOLRVJJ-MLSVHJFASA-N CC(O)C1=C(C)/C2=C/C3=N/C(=C\C4=C(CCC(O)=O)C(C)=C(N4)/C=C4\N=C(\C=C\1/N\2)C(C)=C4C(C)O)/C(CCC(O)=O)=C3C Chemical class CC(O)C1=C(C)/C2=C/C3=N/C(=C\C4=C(CCC(O)=O)C(C)=C(N4)/C=C4\N=C(\C=C\1/N\2)C(C)=C4C(C)O)/C(CCC(O)=O)=C3C UJKPHYRXOLRVJJ-MLSVHJFASA-N 0.000 description 1
- VSEIDZLLWQQJGK-CHOZPQDDSA-N CCC1=C(C)C2=N\C\1=C/C1=C(C)C(C(O)=O)=C(N1)\C(CC(=O)N[C@@H](CC(O)=O)C(O)=O)=C1/N=C(/C=C3\N/C(=C\2)C(C=C)=C3C)[C@@H](C)[C@@H]1CCC(O)=O Chemical compound CCC1=C(C)C2=N\C\1=C/C1=C(C)C(C(O)=O)=C(N1)\C(CC(=O)N[C@@H](CC(O)=O)C(O)=O)=C1/N=C(/C=C3\N/C(=C\2)C(C=C)=C3C)[C@@H](C)[C@@H]1CCC(O)=O VSEIDZLLWQQJGK-CHOZPQDDSA-N 0.000 description 1
- 108010049990 CD13 Antigens Proteins 0.000 description 1
- 102100035893 CD151 antigen Human genes 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 1
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 1
- 101100123850 Caenorhabditis elegans her-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 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
- 241000589876 Campylobacter Species 0.000 description 1
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
- 101710205625 Capsid protein p24 Proteins 0.000 description 1
- 102100025473 Carcinoembryonic antigen-related cell adhesion molecule 6 Human genes 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 0.000 description 1
- 206010039499 Cartilage sarcomas Diseases 0.000 description 1
- 241001660259 Cereus <cactus> Species 0.000 description 1
- 108010078239 Chemokine CX3CL1 Proteins 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 101710164760 Chlorotoxin Proteins 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010008805 Chromosomal abnormalities Diseases 0.000 description 1
- 208000031404 Chromosome Aberrations Diseases 0.000 description 1
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 108010069241 Connexin 43 Proteins 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- SRUWWOSWHXIIIA-UKPGNTDSSA-N Cyanoginosin Chemical compound N1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](C)[C@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C(=C)N(C)C(=O)CC[C@H](C(O)=O)N(C)C(=O)[C@@H](C)[C@@H]1\C=C\C(\C)=C\[C@H](C)[C@@H](O)CC1=CC=CC=C1 SRUWWOSWHXIIIA-UKPGNTDSSA-N 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 102000009512 Cyclin-Dependent Kinase Inhibitor p15 Human genes 0.000 description 1
- 108010009356 Cyclin-Dependent Kinase Inhibitor p15 Proteins 0.000 description 1
- 102000009508 Cyclin-Dependent Kinase Inhibitor p16 Human genes 0.000 description 1
- 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 1
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000000970 DNA cross-linking effect Effects 0.000 description 1
- 102100033587 DNA topoisomerase 2-alpha Human genes 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 102100033553 Delta-like protein 4 Human genes 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- LQKSHSFQQRCAFW-UHFFFAOYSA-N Dolastatin 15 Natural products COC1=CC(=O)N(C(=O)C(OC(=O)C2N(CCC2)C(=O)C2N(CCC2)C(=O)C(C(C)C)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C)C(C)C)C1CC1=CC=CC=C1 LQKSHSFQQRCAFW-UHFFFAOYSA-N 0.000 description 1
- 101100136092 Drosophila melanogaster peng gene Proteins 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 102100039563 ETS translocation variant 1 Human genes 0.000 description 1
- 241000710945 Eastern equine encephalitis virus Species 0.000 description 1
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
- 241001466953 Echovirus Species 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102100036448 Endothelial PAS domain-containing protein 1 Human genes 0.000 description 1
- 241000224431 Entamoeba Species 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 206010014967 Ependymoma Diseases 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
- 241000713730 Equine infectious anemia virus Species 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 108091092566 Extrachromosomal DNA Proteins 0.000 description 1
- 241000272186 Falco columbarius Species 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 102100035427 Forkhead box protein O1 Human genes 0.000 description 1
- 208000032320 Germ cell tumor of testis Diseases 0.000 description 1
- 241000224466 Giardia Species 0.000 description 1
- 108010014663 Glycated Hemoglobin A Proteins 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108091005250 Glycophorins Proteins 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 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
- 208000015023 Graves' disease Diseases 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000724675 Hepatitis E virus Species 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 101000757160 Homo sapiens Aminopeptidase N Proteins 0.000 description 1
- 101000874316 Homo sapiens B melanoma antigen 1 Proteins 0.000 description 1
- 101000874318 Homo sapiens B melanoma antigen 2 Proteins 0.000 description 1
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 1
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000912622 Homo sapiens C-type lectin domain family 12 member A Proteins 0.000 description 1
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
- 101000914326 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 6 Proteins 0.000 description 1
- 101000872077 Homo sapiens Delta-like protein 4 Proteins 0.000 description 1
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 1
- 101000813729 Homo sapiens ETS translocation variant 1 Proteins 0.000 description 1
- 101000877727 Homo sapiens Forkhead box protein O1 Proteins 0.000 description 1
- 101000854520 Homo sapiens Fractalkine Proteins 0.000 description 1
- 101000894966 Homo sapiens Gap junction alpha-1 protein Proteins 0.000 description 1
- 101001074244 Homo sapiens Glycophorin-A Proteins 0.000 description 1
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 1
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 description 1
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 description 1
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 description 1
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 description 1
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101001034314 Homo sapiens Lactadherin Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 1
- 101001005728 Homo sapiens Melanoma-associated antigen 1 Proteins 0.000 description 1
- 101001005718 Homo sapiens Melanoma-associated antigen 2 Proteins 0.000 description 1
- 101001005719 Homo sapiens Melanoma-associated antigen 3 Proteins 0.000 description 1
- 101001005720 Homo sapiens Melanoma-associated antigen 4 Proteins 0.000 description 1
- 101001057131 Homo sapiens Melanoma-associated antigen D4 Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101001024605 Homo sapiens Next to BRCA1 gene 1 protein Proteins 0.000 description 1
- 101000613490 Homo sapiens Paired box protein Pax-3 Proteins 0.000 description 1
- 101000601661 Homo sapiens Paired box protein Pax-7 Proteins 0.000 description 1
- 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 1
- 101000585703 Homo sapiens Protein L-Myc Proteins 0.000 description 1
- 101000798015 Homo sapiens RAC-beta serine/threonine-protein kinase Proteins 0.000 description 1
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 1
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 1
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 1
- 101000809797 Homo sapiens Thymidylate synthase Proteins 0.000 description 1
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 1
- 101000579613 Homo sapiens U6 snRNA-associated Sm-like protein LSm5 Proteins 0.000 description 1
- 241000701149 Human adenovirus 1 Species 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 241000342334 Human metapneumovirus Species 0.000 description 1
- 241000702617 Human parvovirus B19 Species 0.000 description 1
- 108050009363 Hyaluronidases Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 1
- 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000002979 Influenza in Birds Diseases 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 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
- 241000567229 Isospora Species 0.000 description 1
- 241000710842 Japanese encephalitis virus Species 0.000 description 1
- 208000003456 Juvenile Arthritis Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 102100039648 Lactadherin Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 241000219739 Lens Species 0.000 description 1
- 206010024305 Leukaemia monocytic Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 108010010995 MART-1 Antigen Proteins 0.000 description 1
- 102000016200 MART-1 Antigen Human genes 0.000 description 1
- 241001521402 Maackia <angiosperm> Species 0.000 description 1
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 102100025050 Melanoma-associated antigen 1 Human genes 0.000 description 1
- 102100025081 Melanoma-associated antigen 2 Human genes 0.000 description 1
- 102100025082 Melanoma-associated antigen 3 Human genes 0.000 description 1
- 102100025077 Melanoma-associated antigen 4 Human genes 0.000 description 1
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 235000005135 Micromeria juliana Nutrition 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 102100034256 Mucin-1 Human genes 0.000 description 1
- 108010063954 Mucins Proteins 0.000 description 1
- 102000015728 Mucins Human genes 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 231100000678 Mycotoxin Toxicity 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- LYPFDBRUNKHDGX-SOGSVHMOSA-N N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 Chemical compound N1C2=CC=C1\C(=C1\C=CC(=N1)\C(=C1\C=C/C(/N1)=C(/C1=N/C(/CC1)=C2/C1=CC(O)=CC=C1)C1=CC(O)=CC=C1)\C1=CC(O)=CC=C1)C1=CC(O)=CC=C1 LYPFDBRUNKHDGX-SOGSVHMOSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000224436 Naegleria Species 0.000 description 1
- 101000783356 Naja sputatrix Cytotoxin Proteins 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 206010029098 Neoplasm skin Diseases 0.000 description 1
- 108010012255 Neural Cell Adhesion Molecule L1 Proteins 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 102100024964 Neural cell adhesion molecule L1 Human genes 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 1
- IXBQSRWSVIBXNC-HSKGSTCASA-N Nodularin Chemical compound C([C@H](OC)[C@@H](C)\C=C(/C)\C=C\[C@H]1[C@@H](C(=O)N[C@H](CCC(=O)N(C)C(=C\C)/C(=O)N[C@H]([C@H](C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1)C(O)=O)C(O)=O)C)C1=CC=CC=C1 IXBQSRWSVIBXNC-HSKGSTCASA-N 0.000 description 1
- IXBQSRWSVIBXNC-UHFFFAOYSA-N Nodularin Natural products N1C(=O)C(CCCN=C(N)N)NC(=O)C(C)C(C(O)=O)NC(=O)C(=CC)N(C)C(=O)CCC(C(O)=O)NC(=O)C(C)C1C=CC(C)=CC(C)C(OC)CC1=CC=CC=C1 IXBQSRWSVIBXNC-UHFFFAOYSA-N 0.000 description 1
- 241001263478 Norovirus Species 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- VYLQGYLYRQKMFU-UHFFFAOYSA-N Ochratoxin A Natural products CC1Cc2c(Cl)cc(CNC(Cc3ccccc3)C(=O)O)cc2C(=O)O1 VYLQGYLYRQKMFU-UHFFFAOYSA-N 0.000 description 1
- 206010030137 Oesophageal adenocarcinoma Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 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
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229940123973 Oxygen scavenger Drugs 0.000 description 1
- 238000002944 PCR assay Methods 0.000 description 1
- 101150054854 POU1F1 gene Proteins 0.000 description 1
- 102100040891 Paired box protein Pax-3 Human genes 0.000 description 1
- 102100037503 Paired box protein Pax-7 Human genes 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 208000031845 Pernicious anaemia Diseases 0.000 description 1
- 102000006448 Phospholipases A1 Human genes 0.000 description 1
- 102000006447 Phospholipases A2 Human genes 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 101710177166 Phosphoprotein Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 108010047620 Phytohemagglutinins Proteins 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 229910052778 Plutonium Inorganic materials 0.000 description 1
- 101710118150 Podoplanin Proteins 0.000 description 1
- 102100037265 Podoplanin Human genes 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100030128 Protein L-Myc Human genes 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 241000219492 Quercus Species 0.000 description 1
- 102100032315 RAC-beta serine/threonine-protein kinase Human genes 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 102100034027 RNA-binding protein Musashi homolog 2 Human genes 0.000 description 1
- 101710129075 RNA-binding protein Musashi homolog 2 Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- YJDYDFNKCBANTM-QCWCSKBGSA-N SDZ PSC 833 Chemical compound C\C=C\C[C@@H](C)C(=O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C(C)C)NC1=O YJDYDFNKCBANTM-QCWCSKBGSA-N 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000369757 Sapovirus Species 0.000 description 1
- 240000002114 Satureja hortensis Species 0.000 description 1
- 235000007315 Satureja hortensis Nutrition 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 241000607764 Shigella dysenteriae Species 0.000 description 1
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 101710149279 Small delta antigen Proteins 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010068771 Soft tissue neoplasm Diseases 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241001505901 Streptococcus sp. 'group A' Species 0.000 description 1
- 241000193990 Streptococcus sp. 'group B' Species 0.000 description 1
- 108090000058 Syndecan-1 Proteins 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 1
- 201000008717 T-cell large granular lymphocyte leukemia Diseases 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 1
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 1
- 102100035268 T-cell surface protein tactile Human genes 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 102100038618 Thymidylate synthase Human genes 0.000 description 1
- 101710182532 Toxin a Proteins 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 241000224526 Trichomonas Species 0.000 description 1
- 241000223104 Trypanosoma Species 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 102100022563 Tubulin polymerization-promoting protein Human genes 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 108010047933 Tumor Necrosis Factor alpha-Induced Protein 3 Proteins 0.000 description 1
- 102100024596 Tumor necrosis factor alpha-induced protein 3 Human genes 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 102100028261 U6 snRNA-associated Sm-like protein LSm5 Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 240000003864 Ulex europaeus Species 0.000 description 1
- 235000010730 Ulex europaeus Nutrition 0.000 description 1
- 108010041865 Ulex europaeus lectins Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 0.000 description 1
- 241000607626 Vibrio cholerae Species 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
- 241001464837 Viridiplantae Species 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 241000710951 Western equine encephalitis virus Species 0.000 description 1
- 208000026448 Wilms tumor 1 Diseases 0.000 description 1
- 101710127857 Wilms tumor protein Proteins 0.000 description 1
- LQKSHSFQQRCAFW-CCVNJFHASA-N [(2s)-1-[(2s)-2-benzyl-3-methoxy-5-oxo-2h-pyrrol-1-yl]-3-methyl-1-oxobutan-2-yl] (2s)-1-[(2s)-1-[(2s)-2-[[(2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxyl Chemical compound C([C@@H]1N(C(=O)C=C1OC)C(=O)[C@@H](OC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](C(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C)C(C)C)C1=CC=CC=C1 LQKSHSFQQRCAFW-CCVNJFHASA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 201000006966 adult T-cell leukemia Diseases 0.000 description 1
- 239000005409 aflatoxin Substances 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- MXKCYTKUIDTFLY-ZNNSSXPHSA-N alpha-L-Fucp-(1->2)-beta-D-Galp-(1->4)-[alpha-L-Fucp-(1->3)]-beta-D-GlcpNAc-(1->3)-D-Galp Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@@H]([C@@H](NC(C)=O)[C@H](O[C@H]3[C@H]([C@@H](CO)OC(O)[C@@H]3O)O)O[C@@H]2CO)O[C@H]2[C@H]([C@H](O)[C@H](O)[C@H](C)O2)O)O[C@H](CO)[C@H](O)[C@@H]1O MXKCYTKUIDTFLY-ZNNSSXPHSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 235000019728 animal nutrition Nutrition 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 229940049595 antibody-drug conjugate Drugs 0.000 description 1
- CQIUKKVOEOPUDV-IYSWYEEDSA-N antimycin Chemical compound OC1=C(C(O)=O)C(=O)C(C)=C2[C@H](C)[C@@H](C)OC=C21 CQIUKKVOEOPUDV-IYSWYEEDSA-N 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 1
- XADJWCRESPGUTB-UHFFFAOYSA-N apigenin Natural products C1=CC(O)=CC=C1C1=CC(=O)C2=CC(O)=C(O)C=C2O1 XADJWCRESPGUTB-UHFFFAOYSA-N 0.000 description 1
- 229940117893 apigenin Drugs 0.000 description 1
- 235000008714 apigenin Nutrition 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 238000011717 athymic nude mouse Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 206010064097 avian influenza Diseases 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
- 210000004666 bacterial spore Anatomy 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 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
- 235000013361 beverage Nutrition 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 229940053013 bio-mycin Drugs 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000001574 biopsy Methods 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
- 238000009534 blood test Methods 0.000 description 1
- 238000009582 blood typing Methods 0.000 description 1
- 206010006007 bone sarcoma Diseases 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 235000012206 bottled water Nutrition 0.000 description 1
- 229940053031 botulinum toxin Drugs 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- WLZRMCYVCSSEQC-UHFFFAOYSA-N cadmium(2+) Chemical compound [Cd+2] WLZRMCYVCSSEQC-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 238000004364 calculation method Methods 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
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 1
- 231100000677 cardiotoxin Toxicity 0.000 description 1
- 239000002340 cardiotoxin Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000004656 cell transport Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 201000006662 cervical adenocarcinoma Diseases 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 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
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 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
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- 229940088516 cipro Drugs 0.000 description 1
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 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
- CQIUKKVOEOPUDV-UHFFFAOYSA-N citrinine Natural products OC1=C(C(O)=O)C(=O)C(C)=C2C(C)C(C)OC=C21 CQIUKKVOEOPUDV-UHFFFAOYSA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000749 co-immunoprecipitation Methods 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 108010061103 cyclic citrullinated peptide Proteins 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 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
- 108010045552 dolastatin 15 Proteins 0.000 description 1
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 1
- 229940115080 doxil Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 239000000911 dye-antibody conjugate Substances 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 108010018033 endothelial PAS domain-containing protein 1 Proteins 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 231100000317 environmental toxin Toxicity 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 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
- 230000008029 eradication Effects 0.000 description 1
- 229940082789 erbitux Drugs 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 208000028653 esophageal adenocarcinoma Diseases 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 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 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000002211 flavins Chemical class 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960004421 formestane Drugs 0.000 description 1
- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 229960005277 gemcitabine Drugs 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
- 238000001415 gene therapy Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 108091005995 glycated hemoglobin Proteins 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 238000012835 hanging drop method Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 208000025750 heavy chain disease Diseases 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 201000010284 hepatitis E Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 230000007236 host immunity Effects 0.000 description 1
- 102000051957 human ERBB2 Human genes 0.000 description 1
- 238000011577 humanized mouse model Methods 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.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 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 238000003017 in situ immunoassay Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 208000037798 influenza B Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 108040003607 interleukin-13 receptor activity proteins Proteins 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 229940084651 iressa Drugs 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
- 229910052742 iron Inorganic materials 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 208000019420 lymphoid neoplasm Diseases 0.000 description 1
- 201000000564 macroglobulinemia Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 240000004308 marijuana Species 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 229910052752 metalloid Inorganic materials 0.000 description 1
- 150000002738 metalloids Chemical class 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 108010067094 microcystin Proteins 0.000 description 1
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 1
- 229960003248 mifepristone Drugs 0.000 description 1
- 108010071421 milk fat globule Proteins 0.000 description 1
- 230000003278 mimic effect Effects 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
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 238000011242 molecular targeted therapy Methods 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000009343 monoculture Methods 0.000 description 1
- 201000006894 monocytic leukemia Diseases 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 208000010492 mucinous cystadenocarcinoma Diseases 0.000 description 1
- 229940051875 mucins Drugs 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000004220 muscle function Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 239000002636 mycotoxin Substances 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- RIGXBXPAOGDDIG-UHFFFAOYSA-N n-[(3-chloro-2-hydroxy-5-nitrophenyl)carbamothioyl]benzamide Chemical compound OC1=C(Cl)C=C([N+]([O-])=O)C=C1NC(=S)NC(=O)C1=CC=CC=C1 RIGXBXPAOGDDIG-UHFFFAOYSA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229940086322 navelbine Drugs 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 229950006344 nocodazole Drugs 0.000 description 1
- 108010065793 nodularin Proteins 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- RWQKHEORZBHNRI-BMIGLBTASA-N ochratoxin A Chemical compound C([C@H](NC(=O)C1=CC(Cl)=C2C[C@H](OC(=O)C2=C1O)C)C(O)=O)C1=CC=CC=C1 RWQKHEORZBHNRI-BMIGLBTASA-N 0.000 description 1
- DAEYIVCTQUFNTM-UHFFFAOYSA-N ochratoxin B Natural products OC1=C2C(=O)OC(C)CC2=CC=C1C(=O)NC(C(O)=O)CC1=CC=CC=C1 DAEYIVCTQUFNTM-UHFFFAOYSA-N 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000006958 oropharynx cancer Diseases 0.000 description 1
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 1
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 1
- 238000013021 overheating Methods 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
- 239000006179 pH buffering agent Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000002568 pbsc Anatomy 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 201000005528 peripheral nervous system neoplasm Diseases 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- 229950010883 phencyclidine Drugs 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229940109328 photofrin Drugs 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 231100000119 phototoxicity / photoirritation testing Toxicity 0.000 description 1
- 230000001885 phytohemagglutinin Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- 239000003375 plant hormone Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 1
- 229960002169 plerixafor Drugs 0.000 description 1
- 210000004910 pleural fluid Anatomy 0.000 description 1
- OYEHPCDNVJXUIW-UHFFFAOYSA-N plutonium atom Chemical compound [Pu] OYEHPCDNVJXUIW-UHFFFAOYSA-N 0.000 description 1
- 229960001237 podophyllotoxin Drugs 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229910052699 polonium Inorganic materials 0.000 description 1
- HZEBHPIOVYHPMT-UHFFFAOYSA-N polonium atom Chemical compound [Po] HZEBHPIOVYHPMT-UHFFFAOYSA-N 0.000 description 1
- 229920000327 poly(triphenylamine) polymer Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000017363 positive regulation of growth Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 235000021251 pulses Nutrition 0.000 description 1
- JFINOWIINSTUNY-UHFFFAOYSA-N pyrrolidin-3-ylmethanesulfonamide Chemical compound NS(=O)(=O)CC1CCNC1 JFINOWIINSTUNY-UHFFFAOYSA-N 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 201000003804 salivary gland carcinoma Diseases 0.000 description 1
- RPQXVSUAYFXFJA-HGRQIUPRSA-N saxitoxin Chemical compound NC(=O)OC[C@@H]1N=C(N)N2CCC(O)(O)[C@@]22N=C(N)N[C@@H]12 RPQXVSUAYFXFJA-HGRQIUPRSA-N 0.000 description 1
- RPQXVSUAYFXFJA-UHFFFAOYSA-N saxitoxin hydrate Natural products NC(=O)OCC1N=C(N)N2CCC(O)(O)C22NC(N)=NC12 RPQXVSUAYFXFJA-UHFFFAOYSA-N 0.000 description 1
- 239000002795 scorpion venom Substances 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 201000007321 sebaceous carcinoma Diseases 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 208000004548 serous cystadenocarcinoma Diseases 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229940007046 shigella dysenteriae Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- IKEIGECHKXPQKT-UHFFFAOYSA-N silicon phthalocyanine dihydroxide Chemical compound N1=C(C2=CC=CC=C2C2=NC=3C4=CC=CC=C4C(=N4)N=3)N2[Si](O)(O)N2C4=C(C=CC=C3)C3=C2N=C2C3=CC=CC=C3C1=N2 IKEIGECHKXPQKT-UHFFFAOYSA-N 0.000 description 1
- JACPFCQFVIAGDN-UHFFFAOYSA-M sipc iv Chemical class [OH-].[Si+4].CN(C)CCC[Si](C)(C)[O-].C=1C=CC=C(C(N=C2[N-]C(C3=CC=CC=C32)=N2)=N3)C=1C3=CC([C]1C=CC=CC1=1)=NC=1N=C1[C]3C=CC=CC3=C2[N-]1 JACPFCQFVIAGDN-UHFFFAOYSA-M 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- ODJLBQGVINUMMR-HZXDTFASSA-N strophanthidin Chemical compound C1([C@H]2CC[C@]3(O)[C@H]4[C@@H]([C@]5(CC[C@H](O)C[C@@]5(O)CC4)C=O)CC[C@@]32C)=CC(=O)OC1 ODJLBQGVINUMMR-HZXDTFASSA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 201000010965 sweat gland carcinoma Diseases 0.000 description 1
- 201000010740 swine influenza Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229950010924 talaporfin Drugs 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960002197 temoporfin Drugs 0.000 description 1
- 208000002918 testicular germ cell tumor Diseases 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000005676 thermoelectric effect Effects 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-S tobramycin(5+) Chemical compound [NH3+][C@@H]1C[C@H](O)[C@@H](C[NH3+])O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H]([NH3+])[C@H](O)[C@@H](CO)O2)O)[C@H]([NH3+])C[C@@H]1[NH3+] NLVFBUXFDBBNBW-PBSUHMDJSA-S 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940100613 topical solution 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
- 239000003440 toxic substance Substances 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 229930185603 trichostatin Natural products 0.000 description 1
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 238000013414 tumor xenograft model Methods 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- 229950010938 valspodar Drugs 0.000 description 1
- 108010082372 valspodar Proteins 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 229940118696 vibrio cholerae Drugs 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 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
- GBABOYUKABKIAF-IELIFDKJSA-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-IELIFDKJSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.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 CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229940045729 wasp venom protein Drugs 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
- RPQZTTQVRYEKCR-WCTZXXKLSA-N zebularine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=CC=C1 RPQZTTQVRYEKCR-WCTZXXKLSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/44—Sample treatment involving radiation, e.g. heat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
-
- 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
- A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6891—Pre-targeting systems involving an antibody for targeting specific cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0036—Porphyrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
-
- 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
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/405—Concentrating samples by adsorption or absorption
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5002—Partitioning blood components
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/065—Light sources therefor
- A61N2005/0651—Diodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0662—Visible light
- A61N2005/0663—Coloured light
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Radiology & Medical Imaging (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
本願は、2014年8月8日に出願された米国仮出願第62/034,990号に対する優先権を主張する。この出願は、本明細書中に参考として援用される。
本願は、IR700結合体、およびインビボまたはインビトロにおいて標的作用物質を除去する(例えば、分離するかまたは単離する)ためにそれらを使用する方法に関する。例えば、開示されるIR700結合体および方法は、インビボにおいて薬物の薬物動態を制御するための、光によって制御される方法を提供し、それらを用いることにより、環境サンプルもしくは食品サンプルから望まれない作用物質を除去すること、または研究室において標的分子を単離することができる。
複合混合物から生体分子を分離することは、インビボにおいては被験体からまたはインビトロにおいては他のサンプルからトキシン、病原体もしくは薬物を除去することをはじめとした多くの用途において望ましい。さらに、診断方法、環境モニタリングまたは研究の手法をはじめとした多くのインビトロの手法が、複合混合物から分子を分離することまたは単離することに頼っている。現行の技術がありながらも、環境中の(例えば、溶液、細胞および生物全体における)生体分子の混合物の中で、選択された生体分子を改変すること、単離すること、および/または排除することは困難である。
現行の技術がありながらも、環境中の(例えば、溶液、細胞および生物全体における)タンパク質の混合物の中で、選択されたタンパク質または他の標的分子を単離することおよび排除することは困難である。本明細書中に開示される方法は、IR700によって標識された分子、またはそのIR700によって標識された分子と会合した分子のクラスター(例えば、IR700−抗体−抗原複合体)を除去し得るか、または単離し得る。フタロシアニンIRDye700DX(IR700)は、特異的結合剤(例えば、抗体、抗体フラグメント、ハプテン、タンパク質、核酸分子、機能的核酸など)に結合体化されたとき、その特異的結合剤と標的との結合によって標的作用物質を標識するために使用される。同様に、IR700は、薬理学的作用物質または薬物などの分子に結合体化されたとき、例えば被験体における、その作用物質の除去の制御を可能にする。そのIR700色素は、近赤外(NIR)光(例えば、690nm+/−20nm)に曝露されると、切断されて、その分子を親水性から疎水性に変化させ、その分子は凝集する。このことにより、溶液、細胞または生物から標的を除去することが可能になる。さらに、この変化は、IR700−特異的結合剤複合体に結合された標的に影響を及ぼすことができ、ここで、その標的(例えば、タンパク質)は、その機能を失い得、溶液中で凝集物を形成し得、細胞膜を損傷し得、その標的が結合している細胞において細胞傷害性を誘導し得るか、または例えば肝臓におけるマクロファージによってそのような細胞の除去をもたらす。
別段説明されない限り、本明細書中で使用されるすべての専門用語および科学用語は、開示される発明が属する分野の当業者が通常理解している意味と同じ意味を有する。単数形の用語「a」、「an」および「the」は、文脈が明らかに別のことを示していない限り、複数の指示対象を含む。同様に、単語「または」は、文脈が明らかに別のことを示していない限り、「および」を含むと意図される。「含む(Comprising)」は、「含む(including)」を意味する。ゆえに、「AまたはBを含む」は、「Aを含む」または「Bを含む」または「AおよびBを含む」を意味する。
色素IR700は、近赤外(NIR)範囲において励起される光増感剤である。本発明者らは、IR700色素を適切な波長のNIR光に曝露すると、IR700分子の一部が切断されることを明らかにした(図1)。この切断は、その結果として生じる「超疎水性」IR700化合物:
1つまたはそれを超える標的分子または作用物質を、サンプル、例えば、食品サンプル(または供給源)、環境サンプル(または供給源)、発酵サンプルもしくはリアクタサンプル(または供給源)または被験体から得られたサンプルから除去する、例えば、単離するかまたは分離する方法が本明細書中に提供される。例えば、その方法は、少なくとも2つの異なる標的、例えば、少なくとも3つ、少なくとも4つまたは少なくとも5つの異なる標的、例えば、1、2、3、4、5、6、7、8、9または10個の異なる標的をサンプルから除去するためまたは単離するために使用され得る。例えば、少なくとも2つ、少なくとも3つ、少なくとも4つまたは少なくとも5つ(例えば、1、2、3、4、5、6、7、8、9または10個)の異なるIR700分子結合体が、同じサンプルに対して(例えば、同時にまたは一斉に)使用され得、ここで、各々が異なる標的に特異的である。このことにより、複数の標的をサンプルから除去することが可能になる。サンプルから除去され得るかまたは分離され得る例示的な標的としては、タンパク質、ペプチド、レクチン、炭水化物、金属(例えば、重金属)、核酸分子、有機小分子、薬物、毒液、病原体(例えば、ウイルス、寄生生物、細菌または真菌)または細胞(例えば、細胞の混合集団における標的細胞)が挙げられるがこれらに限定されない。いくつかの例において、上記方法は、除去された標的を検出する工程も含む。
標的作用物質を含み得る(または含むと判明しているかまたは含むと疑われる)任意の生物学的検体、食品検体または環境検体が、本明細書中の方法において使用され得る。サンプルには、発酵流体、反応流体(例えば、所望の化合物、例えば、医薬品を生成するために使用されるもの)および組織または臓器の培養流体も含まれ得る。
サンプルが、1つまたはそれを超えるIR700−分子結合体と接触された後、そのサンプルにNIR光が照射される。照射方法は、当該分野で公知である。いくつかの例において、サンプルは、インビトロにおいて、例えば、組織培養皿、試験管、マルチウェルプレート、発酵リアクタ、エッペンドルフチューブ、ペトリ皿、医療用チューブおよびバッグなどにおいて、照射される。いくつかの例において、食品サンプルまたは食料品(例えば、1バッチの乳、果物もしくは野菜の小片または食肉(meat))が照射される。いくつかの例において、環境サンプルまたは環境区域(例えば、ある区域の陸地、水、土壌または空気)が照射される。いくつかの例において、発酵溶液または他の反応溶液(例えば、所望の生成物を生成するもの)が照射される。
上に記載されたインビトロの方法と類似の方法を、インビボにおいて行うことができる。1つまたはそれを超える標的分子または標的作用物質を、被験体、例えば、哺乳動物、例えば、ヒト、マウス、霊長類、ネコ、イヌまたは他の獣医学的被験体から除去する、例えば、単離するかまたは分離する方法が本明細書中に提供される。例えば、その方法は、少なくとも2つの異なる標的、例えば、少なくとも3つ、少なくとも4つまたは少なくとも5つの異なる標的、例えば、1、2、3、4、5、6、7、8、9または10個の異なる標的を被験体から除去するためまたは単離するために使用され得る。例えば、少なくとも2つ、少なくとも3つ、少なくとも4つまたは少なくとも5つ(例えば、1、2、3、4、5、6、7、8、9または10個)の異なるIR700分子結合体が、同じ被験体において(例えば、同時にまたは一斉に)使用され得、ここで、各々が異なる標的に特異的である。このことにより、複数の標的を被験体から除去することが可能になる。被験体から除去され得るか、単離され得るかまたは分離され得る例示的な標的としては、タンパク質、ペプチド、レクチン、炭水化物、金属(例えば、重金属)、核酸分子、有機小分子、薬物(例えば、レクリエーショナルドラッグまたは治療的/薬理学的薬物)、毒液、病原体(例えば、ウイルス、細菌または真菌)または細胞(例えば、細胞の混合集団における細胞、例えば、腫瘍における標的細胞)が挙げられるがこれらに限定されない。いくつかの例において、上記方法は、標的が被験体から除去された後にその除去された標的を検出する工程、処置後の被験体における標的の減少を検出する工程、またはその両方も含む。
いくつかの例において、開示される方法は、被験体から標的を除去するために使用される。1つの例において、IR700−分子結合体は、標的に結合し得るかまたはハイブリダイズし得る特異的結合剤を含む。そのようなIR700−分子結合体は、その標的の存在または量の増加に起因する障害を有する被験体、例えば、標的病原体に感染した者、毒のある動物に噛まれたまたは刺された者、望まれない細胞の存在に起因する障害(例えば、がんまたは自己免疫障害またはアレルギー)を有する者、標的タンパク質、細胞または核酸分子の存在あるいは標的タンパク質、細胞または核酸分子の量の増加に起因する障害を有する者、薬物標的を過剰投与された者などにとって有用である。1つの例において、被験体は、単離されるべき所望の標的抗体、タンパク質、細胞または核酸分子を有する、ヒトまたは実験動物、例えば、ウサギまたはマウスである。
IR700−分子結合体およびさらなる治療薬(例えば、抗新生物剤)は、例えば、細胞が成長している(the cells or growing)成長培地にIR700−分子結合体を加えることによって、インビトロにおいてサンプルと接触され得るか、または例えば、処置されるべき被験体にIR700−分子結合体を投与することによって、インビボにおいて細胞と接触され得る。
被験体および/または細胞は、1つまたはそれを超えるIR700−分子結合体と接触された後に照射される。照射方法は、当該分野で周知である。いくつかの例において、細胞は、被験体から取り出された後に、例えば、組織培養皿または医療用チューブもしくはバッグにおいて(例えば、アフェレーシス中に)、インビトロにおいて照射される。他の例において、被験体は、インビボにおいて照射され、例えば、IR700−分子結合体を予め投与された被験体が照射される。いくつかの例において、被験体の一部分、例えば、臓器が照射されるか、または被験体内の、標的が存在すると疑われる他の区域(例えば、肝臓、心臓、脳または胃)が照射され得る。
装着することができるかまたは身体上に置くことができ、NIR LEDおよび/またはレーザーシステム(例えば、アルゴンNIRレーザー)の組み込みに適用できる、任意のタイプのアイテムが、本明細書中に記載される方法において使用され得る。1つの例において、そのデバイスは、患者に挿入されるチャンバーである。そのようなデバイスは、身体に存在する標的、例えば、血液中もしくはリンパ液中または皮膚における標的を除去するために使用され得る。
本明細書中に記載されるように、開示される方法は、インビボにおいて標的を除去するために使用され得る。いくつかの例において、身体内を循環しているかまたは皮膚に存在する標的を除去するために、患者は、NIR LEDを組み込むデバイスを装着し得る。いくつかの例において、患者は、少なくとも2つのデバイス、例えば、日中に衣料品または宝飾品類および夜間にブランケットを使用する。いくつかの例において、患者は、少なくとも2つのデバイスを同時に、例えば、2つの衣類を使用する。これらのデバイスは、処置がプライベートのままであり、日常の活動に干渉しないように、持ち運びできる日常の衣料品および宝飾品類を用いて患者をNIR光に曝露することを可能にする。いくつかの例において、そのデバイスは、PIT治療のために日中に目立たずに装着され得る。
開示される方法は、インビトロ、エキソビボまたはインビボにおいて、目的の任意の標的作用物質を除去するかまたは単離するためにデザインされ得る。したがって、本明細書中に提供される方法およびIR700−分子結合体は、本明細書中に提供される特定の例などの、目的の任意の標的作用物質を除去するかまたは単離するために使用され得る。例示的な標的作用物質は、下記に提供される;しかしながら、当業者は、開示される方法およびIR700−分子結合体を用いて他の標的作用物質も除去できることを十分に理解する。本明細書中に記載されるように、標的作用物質に結合するかまたはハイブリダイズする適切な特異的結合剤を選択することにより、特定の標的作用物質を除去するか、分離するかまたは単離するためのIR700−特異的結合剤結合体を開発することが可能になる。
1つの例において、標的作用物質は、金属(例えば、高い電気伝導度を有する元素、化合物または合金)、例えば、重金属または栄養金属(nutritional metal)である。したがって、開示される方法およびIR700−分子結合体は、インビボ、エキソビボまたはインビトロにおいて金属の除去を可能にする。金属は、周期表の大部分を占め、非金属元素は、元素周期表の右側にのみ見ることができる。ホウ素(B)からポロニウム(Po)に引かれた斜めの線が、金属と非金属を分ける。この線上のほとんどの元素が、メタロイドであり、時折、半導体と呼ばれる。この区分線の左下の元素は、金属と呼ばれ、この区分線の右上の元素は、非金属と呼ばれる。
任意の病原体または微生物が、本明細書中に提供される方法およびIR700−分子結合体を用いて除去され得るかまたは単離され得る。いくつかの例において、特定の微生物細胞もしくは微生物、特定の胞子または特定のウイルスが除去される。例示的な標的病原体としては、ウイルス、細菌、真菌、線虫および原虫が挙げられるがこれらに限定されない。本明細書中に提供される方法を用いて除去され得るかまたは単離され得る病原体の非限定的なリストは、下記に提供される。
開示される方法およびIR700−分子結合体は、種々のタンパク質およびペプチド、例えば、細胞表面レセプター、サイトカイン、抗体、ホルモン、レクチンならびにトキシンおよび毒液の除去または単離も可能にする。いくつかの例において、疾患または状態に関連する標的タンパク質が選択され、その標的タンパク質の除去または減少は、その疾患または状態を処置するために使用され得る。特定の例において、IR700−分子結合体は、タンパク質またはペプチド標的に特異的に結合し得る(例えば、そのタンパク質に特異的な抗体、機能的抗体フラグメント、Affibody(登録商標)分子、核酸分子、ハプテンまたは機能的核酸を含むIR700−分子結合体)。例えば、特定のタンパク質に対する特異的結合剤は、当該分野で公知である。例えば、そのような抗体は、商業的供給源、例えば、Invitrogen、Santa Cruz Biotechnology(Santa Cruz,CA);ABCam(Cambridge,MA)およびIBL International(Hamburg,Germany)から入手可能である。そのような分子は、標的タンパク質を除去するためのIR700−分子結合体を作製するために使用され得る。
開示される方法は、標的核酸分子、そのようなDNAまたはRNA(例えば、cDNA、ゲノムDNA、mRNA、miRNAなど)、例えば、目的の特定の病原体または細胞に特異的なDNA配列またはRNA配列の除去または単離も可能にする。例えば、病原体は、その病原体に特異的な保存されたDNA配列またはRNA配列を有し得(例えば、保存された配列は、HIV、鳥インフルエンザおよび豚インフルエンザに対して当該分野で公知である)、細胞は、その細胞に特有の特異的なDNA配列またはRNA配列を有し得る。いくつかの例において、疾患または状態に関連する標的核酸分子が選択され、その標的核酸分子の除去または減少は、その疾患または状態を処置する(例えば、発現をダウンレギュレートする)ために使用され得る。1つの例において、標的核酸分子は、サンプルで優位を占めているものであり、ゆえに、サンプルから除去されることにより、そのサンプル中のより稀な核酸分子(例えば、そのサンプル中の稀な生物由来の核酸分子)の解析(例えば、同定またはクローニング)が可能になり得る。
開示される方法およびIR700−分子結合体は、種々の炭水化物(例えば、サッカライド)の除去も可能にする。例としては、単糖類(monosaccarides)および二糖類が挙げられる。特定の例において、炭水化物標的に特異的に結合する特異的結合剤は、レクチンである。例えば、コンカナバリンA、レンチルレクチンおよびスノードロップレクチンが、マンノースを除去するために使用され得;リシン、ピーナッツ凝集素、ジャカリンおよびヘアリーベッチレクチンが、ガラクトースを除去するために使用され得;コムギ胚芽凝集素が、N−アセチルグルコサミンを除去するために使用され得;エルダーベリーレクチンおよびマアキアアムレンシス赤血球凝集素が、N−アセチルノイラミン酸を除去するために使用され得;ハリエニシダ凝集素およびaleuria aurantiaレクチンが、フコースを除去するために使用され得る。そのような分子は、標的炭水化物を除去するためのIR700−分子結合体を作製するために使用され得る。
開示される方法およびIR700−分子結合体は、種々のレクリエーショナルドラッグの除去も可能にする。例えば、そのような薬物は、そのような薬物を過剰投与された被験体から除去され得る。特定の薬物に特異的な抗体は、当該分野で公知である。例えば、テトラヒドロカンナビノール、ヘロイン、コカイン、カフェインおよびメタンフェタミンに対する抗体が、AbCam(Cambridge,MA)から入手可能である。特定の例において、薬物標的に特異的に結合する特異的結合剤は、核酸(例えば、機能的核酸、例えば、アプタマーまたはDNAザイム)である。そのような分子は、標的レクリエーショナルドラッグを除去するためのIR700−分子結合体を作製するために使用され得る。
任意の標的細胞が、開示される方法およびIR700−分子結合体を用いて、インビボ、インビトロまたはエキソビボにおいて除去され得るかまたは単離され得る。被験体から除去されるかまたは単離される標的細胞は、望ましくない細胞もしくはその成長が望まれない細胞(例えば、腫瘍細胞、がん幹細胞、病的な細胞、または被験体において疾患もしくは障害を引き起こすかもしくは悪化させる細胞)であり得るか、または望まれている細胞、例えば、PBMCもしくはHSCであり得る。いくつかの例において、細胞は、表面タンパク質、例えば、その細胞の表面上のレセプターを認識する特異的結合剤を使用することによって除去されるかまたは単離される。例えば、標的細胞は、他の非標的細胞の表面上には実質的に見出されない細胞表面タンパク質を発現し得、そのようなタンパク質を特異的に認識する特異的結合剤が選択され得、IR700−分子結合体が、そのタンパク質に対して生成され得る。例えば、特定の細胞および細胞表面タンパク質に特異的な抗体および機能的核酸分子が、当該分野で公知であり、商業的供給源、例えば、AbCamおよびSanta Cruz Biotechnologyから入手可能である。
いくつかの例において、標的は、薬物動態が制御されるべき薬物である。例えば、その薬物は、所望の治療効果を有するがそれが身体内に長時間存在することは望ましくない場合がある薬理学的薬物(例えば、処方箋薬または薬局から入手可能なもの)であり得る。開示される方法およびIR700−薬物結合体は、所望の長さの時間が経過した後、例えば、その薬物が所望の治療効果を有した後に、結合体化された医薬品を身体から除去することを可能にする。例えば、IR700−薬物結合体は、その薬物が所望の効果を有するのに十分な時間にわたって被験体に有効量で投与され得る。次いで、IR700−薬物複合体が凝集するのを可能にする条件下において、その被験体にNIR光が照射される。結果として生じた凝集物が、除去されるか、または身体によって、例えば肝臓によって分解され、それにより、その薬物が身体から除去される(またはその薬物が不活性になる)。いくつかの例において、被験体には、IR700−薬物複合体の投与とそれに続くNIR光への曝露の複数回の繰り返し(multiple rounds)、例えば、少なくとも2回、少なくとも3回、少なくとも4回、少なくとも5回、少なくとも6回、少なくとも7回、少なくとも8回、少なくとも9回、少なくとも10回もしくは少なくとも20回またはそれを超えるそのような処置の繰り返しが行われる。
IR700−分子複合体における分子は、特異的結合剤と標的作用物質との選択的結合を可能にする特異的結合剤であり得る。特異的結合剤は、当該分野で公知であり、非限定的な例が下記に提供される。例えば、IR700−分子結合体は、IR700−抗体結合体、IR700−抗体フラグメント結合体、IR700−Affibody(登録商標)分子結合体、IR700−ハプテン結合体、IR700−レクチン結合体、IR700−タンパク質結合体、IR700−核酸分子結合体またはIR700−機能的核酸結合体であり得、ここで、その抗体、抗体フラグメント、Affibody(登録商標)分子、ハプテン、レクチン、タンパク質、核酸分子および機能的核酸は、標的分子に特異的に結合し得る。商業的に入手可能な特異的結合剤およびそれらを作製するための公知の方法は、任意のIR700−特異的結合剤複合体を作製することを可能にする。例えば、数多くの作用物質、例えば、タンパク質(例えば、サイトカイン、腫瘍抗原など)、金属、有機小化合物および核酸分子に対する抗体(およびその機能的フラグメント)、DNAザイムおよびアプタマーが入手可能である。さらに、特定の標的に特異的な抗体、機能的核酸および核酸分子を作製する方法は、当該分野で周知である。
様々な分子に特異的な抗体および抗体フラグメントが、当該分野で周知である。したがって、いくつかの例において、IR700−分子複合体における分子は、抗体または抗体フラグメントと標的(例えば、標的タンパク質)との特異的結合を可能にする、抗体またはそのフラグメントである。本明細書中に提供される方法において使用され得る抗体には、インタクトな免疫グロブリン、バリアント免疫グロブリンおよび抗体の一部、例えば、天然に存在する抗体または組換え抗体の抗原結合フラグメントが含まれる。
様々な標的に特異的なAffibody(登録商標)分子が当該分野で周知である(例えば、Affibody,Sona,Sweden製のもの)。したがって、いくつかの例において、IR700−分子複合体における分子は、Affibody(登録商標)分子と標的(例えば、標的タンパク質)との特異的結合を可能にする、Affibody(登録商標)分子である。Affibody(登録商標)分子は、約6kDaの低分子タンパク質抗体模倣物である。いくつかの例において、Affibody(登録商標)分子は、58アミノ酸を有する3つのアルファヘリックスからなる。対照的に、mAbは、約150kDaであり、単一ドメイン抗体は、約12〜15kDaである。ユニークな結合特性を有するAffibody(登録商標)分子は、通常、親タンパク質ドメインの結合活性に関与する2つのアルファ−ヘリックスに位置する13個のアミノ酸のランダム化によって生成される。いくつかの例において、結合表面の外側のアミノ酸は、その骨格において置換されて、先祖のプロテインAドメインと全く異なる表面をもたらす。標的タンパク質に結合する特定のAffibody(登録商標)分子は、数十億個の異なるバリアントを含むプール(ライブラリー)から、ファージディスプレイを用いて「釣り上げられ」得る。
ハプテンは、より大きなキャリア(例えば、タンパク質)に結合されたとき、通常、免疫応答の誘発だけを行い得る小分子である。ハプテンは、不完全な抗原または部分的な抗原として当該分野で公知である。しかし、ハプテンは、抗体と同様に標的分子に結合し得るので、いくつかの例において、IR700−分子複合体における分子は、ハプテンであり、そのハプテンと標的(例えば、標的タンパク質)との特異的結合が可能になる。
1つの例において、特異的結合剤は、レクチンである。レクチンは、特定の炭水化物、例えば、細胞の表面上の炭水化物を認識してそれに結合するタンパク質である。したがって、いくつかの例において、IR700−分子複合体における分子は、レクチンであり、そのレクチンと標的炭水化物との特異的結合が可能になる。レクチンは、IR700への結合体化/結合を可能にするタンパク質またはペプチド伸長物を含むように改変され得る。
1つの例において、特異的結合剤は、タンパク質である。特定のタンパク質、核酸分子および他の結合パートナーを認識してそれに結合するタンパク質が使用され得る。例えば、タンパク質リガンドは、細胞表面上の特定のレセプタータンパク質に結合するために使用され得る。したがって、いくつかの例において、IR700−分子複合体における分子は、タンパク質であり、そのタンパク質と標的タンパク質、核酸分子または他の結合分子との特異的結合およびそのタンパク質に結合する分子(例えば、そのタンパク質と共有結合を形成する分子)の除去が可能になる。
1つの例において、特異的結合剤は、核酸分子である。特定のタンパク質、核酸分子(ハイブリダイゼーションを介して)および他の結合パートナーを認識してそれに結合する核酸分子が使用され得る。例えば、標的核酸分子に対して十分な相補性を有する核酸分子は、その相補的な配列にハイブリダイズし、その相補的な配列を除去し得る。したがって、いくつかの例において、IR700−分子複合体における分子は、核酸分子であり、その核酸分子と標的タンパク質、核酸分子または他の結合分子との特異的結合、およびその核酸分子に結合する分子の除去が可能になる。
1つの例において、特異的結合剤は、機能的核酸分子(FNA)(Liuら、Chem.Rev.2009,109,1948−1998)である。DNAザイムおよびDNAアプタマーを含むFNAは、広範囲の標的を認識してそれに高親和性かつ高特異性で結合する核酸分子(例えば、DNAまたはRNA)である。したがって、いくつかの例において、IR700−分子複合体における分子は、FNAであり、そのFNAと標的との特異的結合、およびそのFNAに結合する標的の除去が可能になる。
IRDye700結合体化トラスツズマブ(抗Her2)の合成
IRDye700に結合体化されたVectibix(登録商標)(抗HER1)の合成
IRDye700に結合体化されたHuJ591の合成
IRDye700に結合体化されたセツキシマブの合成
NIRへの曝露後のIR700の切断
IR700はNIRへの曝露後に蛍光を失わない
IR700は酸素の非存在下でNIRによって切断され得る
酸素飽和はNIRによるIR700の切断を減少させ得る
切断されたIR700のインビボ輸送
材料および方法
水溶性のケイ素−フタロシアニン誘導体であるIRDye700DX NHSエステルは、LI−COR Bioscience(Lincoln,NE,USA)製であった。EGFRに対して誘導された完全ヒト化IgG2 mAbであるパニツムマブは、Amgen(Thousand Oaks,CA,USA)製であった。HER2に対して誘導された95%ヒト化IgG1 mAbであるトラスツズマブは、Genentech(South San Francisco,CA,USA)製であった。他のすべての化学物質は、試薬グレードであった。
色素とmAbとの結合体化は、以前の報告(Mitsunagaら、Nat.Med.17,1685−1691,2011;Satoら、Mol.Oncol.8,620−632,2014)に従って行った。簡潔には、パニツムマブ、トラスツズマブまたは抗PSMA ab(1mg,6.8nmol)を、0.1mol/L Na2HPO4(pH8.6)中において室温で1時間、IR700 NHSエステル(60.2μg,30.8nmol)とともにインキュベートした。その混合物を、Sephadex G50カラム(PD−10;GE Healthcare,Piscataway,NJ,USA)を用いて精製した。タンパク質濃度を、分光法(8453 Value System;Agilent Technologies,Santa Clara,CA,USA)を用いて595nmにおける吸収を測定することによって、Coomassie Plusタンパク質アッセイキット(Thermo Fisher Scientific Inc,Rockford,IL,USA)を用いて決定した。各mAbに結合体化されたIR700分子の数を確認するために、分光法を用いて、IR700の濃度を689nmにおける吸収によって測定した。その合成は、平均4つのIR700分子が単一の抗体に結合されるように制御された。SDS−PAGEを、以前に報告されたように(Sanoら、ACS Nano 7,717−724,2013)、各結合体に対する品質管理として用いた。トラスツズマブに結合体化されたIR700は、Tra−IR700と省略され、パニツムマブに結合体化されたIR700は、Pan−IR700と省略され、抗PSMA抗体に結合体化されたIR700は、PSMA−IR700と省略される。
GFPおよびルシフェラーゼを安定に発現するA431細胞、3T3/HER2細胞(HER2を安定に発現するBalb/3T3細胞)またはPC3−PIP細胞(PSMAを安定に発現するPC3細胞)を、RediFect Red−FLuc−GFP(PerkinElmer,Waltham,MA,USA)のトランスフェクションによって樹立した。GFPおよびルシフェラーゼの高発現が、継代数10において確認された。RFPを安定に発現するBalb/3T3細胞を、RFP(EF1a)−Puroレンチウイルス粒子(AMSBIO,Cambridge,MA,USA)によるトランスフェクションによって樹立した。RFPの高発現を、継代数10において選択剤の非存在下で確認した。これらの細胞は、それぞれA431−luc−GFP、3T3/Her2−luc−GFP、PC3−PIP−luc−GFP、Balb/3T3−RFPと省略される。細胞は、37℃、95%大気および5%二酸化炭素の雰囲気の加湿恒温器内の組織培養フラスコ内の、10%ウシ胎児血清および1%ペニシリン/ストレプトマイシン(Life Technologies)が補充されたRPMI1640(Life Technologies,Gaithersburg,MD,USA)において成長させた。
5000個の細胞を50μLの培地に懸濁し、次いで、製造者の指示に従って96ウェルプレート(3D Biomatrix Inc,Ann Arbor,MI,USA)に分注するハンギングドロップ法によって、球状体を生成した(Satoら、Mol.Oncol.8,620−632,2014)。混合された球状体を、5,000個のBalb/3T3−RFP細胞および500個のA431−luc−GFP細胞(100:10))を用いて作製した。観察または処理の後、球状体を再度、新しい培地を含むハンギングドロッププレートでインキュベートした。それらの球状体の体積を、式:球状体積=4/3π×半径3を用いて算出した。
APC剤とのインキュベーション後の細胞から生じる蛍光を、フローサイトメーター(FACS Calibur,BD BioSciences,San Jose,CA,USA)およびCellQuestソフトウェア(BD BioSciences)を用いて測定した。細胞(1×105個)を、37℃において6時間にわたって各APCとともにインキュベートした。結合体化された抗体の特異的結合を検証するために、過剰量の抗体(50μg)を使用して、0.5μgの色素−抗体結合体をブロックした(Satoら、Mol.Oncol.8,620−632,2014)。
IR700結合体の抗原特異的局在化を検出するために、蛍光顕微鏡法を行った(IX61またはIX81;Olympus America,Melville,NY,USA)。10000個の細胞を、底がカバーガラスのディッシュ上に播種し、24時間インキュベートした。次いで、APCをその培養培地に10μg/mLで加え、37℃で6時間インキュベートした。次いで、それらの細胞をPBSで洗浄し;ヨウ化プロピジウム(PI)(1:2000)(Life Technologies)およびCytox Blue(1:500)(Life Technologies)を使用して、死細胞を検出した。これらを、観察の30分前の培地に加えた。次いで、それらの細胞をNIR光に曝露し、連続的な像を得た。590〜650nm励起フィルターおよび665〜740nm帯域発光フィルターを用いてフィルターをセットし、IR700蛍光を検出した。
20万個のA431−luc−GFP細胞を24ウェルプレートに播種するか、または2000万個の細胞を10cmディッシュ上に播種し、24時間インキュベートした。培地を、10μg/mLのtra−IR700を含む新鮮培養培地に交換し、それを37℃で6時間インキュベートした。PBSで洗浄した後、フェノールレッドフリー培養培地を加えた。次いで、細胞に、670〜710nm波長の光を放射するNIRレーザー(L690−66−60;Marubeni America Co.,Santa Clara,CA,USA)を照射した。実際の出力密度(mW/cm2)を光パワーメータ(PM100,Thorlabs,Newton,NJ,USA)で測定した。
APCによるPITの細胞傷害作用を、ルシフェラーゼ活性およびフローサイトメトリーPI染色またはGFPによって決定した。ルシフェラーゼ活性に対しては、150μg/mLのD−ルシフェリン含有培地(Gold Biotechnology,St Louis,MO,USA)を、PITの1時間後に、PBSで洗浄した細胞に投与し、生物発光イメージング(BLI)システム(Photon Imager;Biospace Lab,Paris,France)において解析した。フローサイトメトリーアッセイに対しては、細胞を、処理の1時間後にトリプシン処理し、PBSで洗浄した。その細胞懸濁液にPIを加え(最終2μg/mL)、室温において30分間インキュベートした後、フローサイトメトリーを行った。
20万個の細胞を、底がカバーガラスのディッシュ上に播種し、12時間インキュベートした。次いで、APCをその培地(フェノールレッドフリー)に10μg/mLで加え、37℃で6時間インキュベートした。それらの細胞をPBSで洗浄し、培地を新しいフェノールレッドフリー培地に交換し、カバーガラスの下側にマークをつけた(それによって観察位置を決定した)。PITの1時間後に、細胞を再度観察した。GFP/RFP強度を、各球状体20の同じ視野において同じ閾値を用いて総画素数で評価した。像の解析を、ImageJソフトウェア(http://rsb.info.nih.gov/ij/)を用いて行った。処理された細胞からの蛍光を、フローサイトメーター(FACS Calibur)を用いて測定した。
すべてのインビボ手技が、Guide for the Care and Use of Laboratory Animal Resources(1996),US National Research Councilに従って行われ、地域のAnimal Care and Use Committeeによって承認された。6〜8週齢の雌のホモ接合体無胸腺ヌードマウスをCharles River(NCI−Frederick)から購入した。手技の間、マウスをイソフルランで麻酔にかけた。
100μgのpan−IR700をマウスに注射するか、または以下のとおりマウスを照射した:(1)注射後の1日目に50J/cm2のNIR光を投与し、2日目に右の腫瘍に100J/cm2のNIR光を投与し、(2)左の腫瘍にはNIR光を投与せず、該腫瘍は、コントロールとして働き、保護物(shield)であった。コントロールには、(1)1日目に50J/cm2のNIR光を曝露し、2日目に右の腫瘍に100J/cm2のNIR光を曝露するだけのもの;(2)左の腫瘍に対する処置がないものが含まれた。これらの治療は、細胞移植後の7日目に一度だけ行われた。マウスを毎日モニターし、連続的な画像解析を行った。
IR700蛍光を検出するためにPearl Imager(LI−COR Bioscience)およびGFP/RFPのためにMaestro Imager(CRi,Woburn,MA,USA)を用いて、インビボ蛍光像を得た。GFP/RFPの場合、GFPに対しては445〜490nmの帯域フィルター(励起)および515nm超のロングパスブルーフィルター(発光)、RFPに対しては503〜555nm(励起)および580nm超のロングパスグリーンフィルターをそれぞれ使用した。調整可能な発光フィルターを、一定の曝露(800msec)で515nmから580nmまで10nmずつ自動的に上げた。蛍光スペクトル像は、自己蛍光スペクトルおよびGFP/RFP(腫瘍)からのスペクトルからなり、それらを、Maestroソフトウェア(CRi)を用いてGFPの特徴的なスペクトルパターンに基づいて分離した(unmixed)。そのモデルに適切であるように、側腹部の腫瘍におけるまたは腹部領域にわたる関心領域(ROI)を手動で描写し(manually drawn)、蛍光強度を測定した。
BLIの場合、D−ルシフェリン(15mg/mL,200μL)を腹腔内に注射し、6日目にPhoton Imagerを用いてルシフェラーゼ活性についてマウスを解析した。さらなる研究のために、腫瘍サイズおよび生物発光に基づいてマウスを選択した。ルシフェラーゼ活性を定量するために、同様のサイズのROIを腫瘍全体にわたって配置した。
データは、別段示されない限り、最低4回の実験からの平均値±s.e.m.として表わされる。統計プログラム(GraphPad Prism;GraphPad Software,La Jolla,CA,USA)を用いて、統計解析を行った。
細胞の部分集団の選択的死滅化
Claims (24)
- サンプルから標的を除去する方法であって、該方法は、
該サンプルをIR700−分子結合体と接触させることにより、IR700−分子結合体−標的複合体を形成する工程であって、ここで、該IR700−分子結合体の分子は、該標的に特異的に結合する特異的結合剤を含む、工程;
疎水性IR700−分子結合体−標的複合体を生成するのに十分な条件下において、660〜710nmの波長かつ少なくとも1J cm−2の線量で該サンプルに照射する工程;
該疎水性IR700−分子結合体−標的複合体の凝集を可能にする条件下において該サンプルをインキュベートする工程;および
該疎水性IR700−分子結合体−標的複合体を該サンプルから分離し、それにより、該標的を該サンプルから除去する工程
を含む、方法。 - 前記標的が、タンパク質、ペプチド、レクチン、炭水化物、金属、核酸分子、レクリエーショナルドラッグ、有機小分子、病原体、胞子または細胞である、請求項1に記載の方法。
- 前記IR700−分子結合体が、IR700−抗体結合体、IR700−抗体フラグメント結合体、IR700−Affibody(登録商標)分子結合体、IR700−ハプテン結合体、IR700−レクチン結合体、IR700−タンパク質結合体、IR700−核酸分子結合体またはIR700−機能的核酸結合体を含み、ここで、該抗体、抗体フラグメント、Affibody(登録商標)分子、ハプテン、レクチン、タンパク質、核酸分子および該機能的核酸は、前記標的分子に特異的に結合し得る、請求項1または2に記載の方法。
- 前記サンプルが、食品サンプル、環境サンプル、リアクタサンプル、発酵サンプルまたは被験体から得られたサンプルである、請求項1〜3のいずれかに記載の方法。
- 前記サンプルが、690nm+/−20nmまたは690nm+/−4nmの波長で照射される、請求項1〜4のいずれかに記載の方法。
- 前記疎水性IR700−分子結合体−標的分子複合体の凝集を可能にする条件下において前記サンプルをインキュベートする工程が、該疎水性IR700−分子結合体−標的分子複合体がペレットを形成するのを可能にする条件下において該サンプルを遠心分離する工程を含む、請求項1〜5のいずれかに記載の方法。
- 前記疎水性IR700−分子結合体−標的分子複合体の凝集を可能にする条件下において前記サンプルをインキュベートする工程が、該疎水性IR700−分子結合体−標的分子複合体が容器の底に沈降するのを可能にする工程を含む、請求項1〜5のいずれかに記載の方法。
- 前記疎水性IR700−分子結合体−標的分子複合体を前記サンプルから分離する工程が、該疎水性IR700−分子結合体−標的分子複合体の凝集を可能にした後、上清を除去する工程を含む、請求項1〜7のいずれかに記載の方法。
- 前記サンプルから除去された前記標的を測定する工程をさらに含む、請求項1〜8のいずれかに記載の方法。
- 前記標的に結合した他の分子を検出する工程をさらに含む、請求項1〜9のいずれかに記載の方法。
- 標的分子を被験体から除去する方法であって、該方法は、
治療有効量のIR700−分子結合体を被験体に投与する工程であって、ここで、該IR700−分子結合体の分子は、該標的分子を含むか、または該分子は、該標的に特異的に結合する特異的結合剤を含む、工程;
疎水性IR700−分子結合体を形成する条件下において、660nm〜710nmの波長かつ少なくとも4J cm−2の線量で該被験体に照射する工程;
該疎水性IR700−分子結合体の凝集を可能にする工程;
該疎水性IR700−分子結合体が該被験体から除去されることを可能にし、それにより、該標的分子を該被験体から除去する工程;および
該被験体における該標的分子の量の減少を検出するかまたは該被験体から除去された該標的分子の量の増加を検出する工程
を含む、方法。 - 前記標的が、タンパク質、ペプチド、レクチン、炭水化物、金属、核酸分子、有機小分子、レクリエーショナルドラッグ、病原体、胞子、細胞または薬理学的作用物質である、請求項11に記載の方法。
- 前記標的細胞が、腫瘍における細胞である、請求項12に記載の方法。
- 前記腫瘍における前記細胞が、腫瘍細胞、免疫細胞またはがん幹細胞である、請求項13に記載の方法。
- 前記標的細胞が、負の調節性T細胞である、請求項12に記載の方法。
- 前記負の調節性T細胞が、CD4+CD25+FoxP3+T細胞であり、前記IR700−分子結合体が、抗CD25抗体または抗CLTA4抗体を含む、請求項15に記載の方法。
- 前記IR700−分子結合体が、前記標的分子を含み、該標的分子は、薬理学的作用物質を含む、請求項12に記載の方法。
- 前記薬理学的作用物質が、化学療法剤、生物学的薬剤、抗生物質、抗高血圧剤、抗うつ剤、鎮痛剤、生殖ホルモン、血液希釈剤、ステロイドまたはスタチンを含む、請求項17に記載の方法。
- 前記IR700−分子結合体が、IR700−抗体結合体、IR700−抗体フラグメント結合体、IR700−Affibody(登録商標)分子結合体、IR700−ハプテン結合体、IR700−レクチン結合体、IR700−タンパク質結合体、IR700−核酸分子結合体またはIR700−機能的核酸結合体を含み、ここで、該抗体、抗体フラグメント、Affibody(登録商標)分子、ハプテン、レクチン、タンパク質、核酸分子および該機能的核酸は、前記標的分子に特異的に結合し得る、請求項11に記載の方法。
- 前記被験体が、690nm+/−20nmまたは690nm+/−4nmの波長で照射される、請求項11〜19のいずれかに記載の方法。
- 前記被験体に照射する工程が、該被験体が装着したデバイスを用いる工程を含み、該デバイスは、近赤外(NIR)発光ダイオード(LED)を備える、請求項11〜20のいずれかに記載の方法。
- 前記被験体が、乳房、肝臓、腎臓、子宮、結腸、卵巣、前立腺、膵臓、脳、頚部、骨、皮膚または肺のがんを有する、請求項11〜21のいずれかに記載の方法。
- 前記疎水性IR700−分子結合体が前記被験体から除去されることを可能にする工程が、該疎水性IR700−分子結合体が肝臓に到達して分解されることを可能にし、それにより、該標的分子を該被験体から除去することを含む、請求項11〜22のいずれかに記載の方法。
- 前記被験体における前記標的分子の量の減少を検出する工程が、該被験体から得られた血液サンプル中の該標的の量を測定することを含む、請求項11〜23のいずれかに記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462034990P | 2014-08-08 | 2014-08-08 | |
US62/034,990 | 2014-08-08 | ||
PCT/US2015/044168 WO2016022896A1 (en) | 2014-08-08 | 2015-08-07 | Photo-controlled removal of targets in vitro and in vivo |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020068338A Division JP7075435B2 (ja) | 2014-08-08 | 2020-04-06 | インビトロおよびインビボにおける標的の光制御除去 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2017524002A true JP2017524002A (ja) | 2017-08-24 |
JP2017524002A5 JP2017524002A5 (ja) | 2018-08-02 |
JP6796058B2 JP6796058B2 (ja) | 2020-12-02 |
Family
ID=54065450
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017506895A Active JP6796058B2 (ja) | 2014-08-08 | 2015-08-07 | インビトロおよびインビボにおける標的の光制御除去 |
JP2020068338A Active JP7075435B2 (ja) | 2014-08-08 | 2020-04-06 | インビトロおよびインビボにおける標的の光制御除去 |
JP2022079474A Pending JP2022116064A (ja) | 2014-08-08 | 2022-05-13 | インビトロおよびインビボにおける標的の光制御除去 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020068338A Active JP7075435B2 (ja) | 2014-08-08 | 2020-04-06 | インビトロおよびインビボにおける標的の光制御除去 |
JP2022079474A Pending JP2022116064A (ja) | 2014-08-08 | 2022-05-13 | インビトロおよびインビボにおける標的の光制御除去 |
Country Status (9)
Country | Link |
---|---|
US (2) | US10830678B2 (ja) |
EP (1) | EP3177323B2 (ja) |
JP (3) | JP6796058B2 (ja) |
CN (2) | CN106470705B (ja) |
AU (2) | AU2015300915B2 (ja) |
CA (1) | CA2954463C (ja) |
ES (1) | ES2743458T5 (ja) |
SG (1) | SG11201610052TA (ja) |
WO (1) | WO2016022896A1 (ja) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019172110A1 (ja) * | 2018-03-09 | 2019-09-12 | 学校法人慈恵大学 | 血管を標的とする抗体と光増感剤とのコンジュゲート |
WO2020246350A1 (ja) * | 2019-06-03 | 2020-12-10 | 学校法人慈恵大学 | 殺菌剤 |
US11141483B2 (en) | 2015-08-18 | 2021-10-12 | Rakuten Medical, Inc. | Methods for manufacturing phthalocyanine dye conjugates and stable conjugates |
US11147875B2 (en) | 2015-08-18 | 2021-10-19 | Rakuten Medical, Inc. | Compositions, combinations and related methods for photoimmunotherapy |
JP2021530558A (ja) * | 2018-06-21 | 2021-11-11 | 株式会社島津製作所 | 近赤外光免疫療法による治療法を試験するための方法 |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8524239B2 (en) | 2010-07-09 | 2013-09-03 | The United States of America as represented by the Secrectary, Department of Health and Human Services | Photosensitizing antibody-fluorophore conjugates |
SG11201610052TA (en) * | 2014-08-08 | 2017-02-27 | Us Health | Photo-controlled removal of targets in vitro and in vivo |
EP3331909A1 (en) | 2015-08-07 | 2018-06-13 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Near infrared photoimmunotherapy (nir-pit) of suppressor cells to treat cancer |
US11832801B2 (en) * | 2016-07-11 | 2023-12-05 | Arizona Board Of Regents On Behalf Of Arizona State University | Sweat as a biofluid for analysis and disease identification |
US20190184015A1 (en) * | 2016-09-02 | 2019-06-20 | European Molecular Biology Laboratory | Irradiation treatment of neurological sensations by photoablation |
AU2018225177A1 (en) * | 2017-02-23 | 2019-09-05 | Rakuten Medical, Inc. | Therapeutic compositions and related methods for photoimmunotherapy |
CN106996892A (zh) * | 2017-03-28 | 2017-08-01 | 四川出入境检验检疫局检验检疫技术中心 | 食品接触片材特定迁移试验采样浸泡装置 |
CN114423453A (zh) * | 2019-07-30 | 2022-04-29 | 乐天医药生技股份有限公司 | 使用偶联的抗cd25酞菁和抗pd1的基于光化学的癌症疗法近红外(nir)光免疫疗法(pit) |
MX2022001515A (es) * | 2019-08-07 | 2022-04-06 | Rakuten Medical Inc | Composiciones de conjugado de cetuximab-ir700. |
CN111150844B (zh) * | 2020-01-10 | 2022-08-19 | 康宏耀源(天津)科技有限公司 | 抗her2亲合体靶向光敏剂的合成和应用 |
JP2021129555A (ja) * | 2020-02-18 | 2021-09-09 | 株式会社島津製作所 | 細胞精製装置および細胞精製方法 |
US20230190934A1 (en) * | 2020-05-14 | 2023-06-22 | Rakuten Medical, Inc. | Methods and compositions for treating a tumor |
CN116102741B (zh) * | 2023-04-10 | 2023-06-20 | 中国农业科学院农业质量标准与检测技术研究所 | 脱除蜂毒致敏原用的磁性纳米复合材料及制备方法和应用 |
CN116592899B (zh) * | 2023-04-28 | 2024-03-29 | 哈尔滨工业大学 | 一种基于模块化红外靶标的位姿测量系统 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013009475A1 (en) * | 2011-07-11 | 2013-01-17 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Photosensitizing antibody-phuorophore conjugates |
Family Cites Families (97)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE547020A (ja) | 1955-04-20 | |||
US4444487A (en) | 1979-07-02 | 1984-04-24 | Xerox Corporation | Multiple-flash fuser |
GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4745055A (en) | 1985-05-07 | 1988-05-17 | California Biotechnology Inc. | Fused protein for enzyme immunoassay system |
CA1340456C (en) | 1986-07-07 | 1999-03-23 | Hubert J.P. Schoemaker | Chimeric rodent/human immunoglobulins specific for tumor-associated antigens |
GB8626412D0 (en) | 1986-11-05 | 1986-12-03 | Clark M R | Antibodies |
US5494793A (en) | 1986-12-15 | 1996-02-27 | British Technology Group Usa Inc. | Monomeric phthalocyanine reagents |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5196005A (en) | 1991-11-26 | 1993-03-23 | Pdt Systems, Inc. | Continuous gradient cylindrical diffusion tip for optical fibers and method for making |
ATE181551T1 (de) | 1992-04-17 | 1999-07-15 | Abbott Lab | Taxol-derivate |
US6667156B2 (en) | 1995-12-27 | 2003-12-23 | Uab Research Foundation | Diagnosis and treatment of neuroectodermal tumors |
US7521531B2 (en) | 1996-08-28 | 2009-04-21 | Immunomedics, Inc. | Methods for the purification of stable radioiodine conjugates |
US5912264A (en) | 1997-03-03 | 1999-06-15 | Bristol-Myers Squibb Company | 6-halo-or nitrate-substituted paclitaxels |
DE19717904A1 (de) | 1997-04-23 | 1998-10-29 | Diagnostikforschung Inst | Säurelabile und enzymatisch spaltbare Farbstoffkonstrukte zur Diagnostik mit Nahinfrarotlicht und zur Therapie |
US6344050B1 (en) | 1998-12-21 | 2002-02-05 | Light Sciences Corporation | Use of pegylated photosensitizer conjugated with an antibody for treating abnormal tissue |
MXPA02001911A (es) * | 1999-08-24 | 2003-07-21 | Medarex Inc | Anticuerpos ctla-4 humanos y sus usos. |
JP2003519796A (ja) | 2000-01-12 | 2003-06-24 | ヴェンタナ メディカル システムズ インコーポレイテッド | 画像分析によるタンパク質の定量法 |
CA2399967A1 (en) | 2000-02-01 | 2001-08-09 | Dwight W. Miller | Methods for predicting the biological, chemical, and physical properties of molecules from their spectral properties |
CO5280224A1 (es) | 2000-02-02 | 2003-05-30 | Univ Florida State Res Found | Taxanos sustituidos con ester en c7, utiles como agentes antitumorales y composiciones farmaceuticas que los contienen |
US6706474B1 (en) | 2000-06-27 | 2004-03-16 | Board Of Trustees Of The University Of Illinois | Nucleic acid enzyme biosensors for ions |
WO2002100326A2 (en) | 2001-05-01 | 2002-12-19 | The General Hospital Corporation | Photoimmunotherapies for cancer using photosensitizer immunoconjugates and combination therapies |
JP2005500034A (ja) | 2001-06-20 | 2005-01-06 | プロション バイオテク リミテッド | 受容体型タンパク質チロシンキナーゼ活性化を遮断する抗体、そのスクリーニング方法、及びその使用 |
US20030031627A1 (en) | 2001-07-31 | 2003-02-13 | Mallinckrodt Inc. | Internal image antibodies for optical imaging and therapy |
US20030105299A1 (en) | 2001-10-17 | 2003-06-05 | Mallinckrodt Inc. | Carbocyanine dyes for tandem, photodiagnostic and therapeutic applications |
JP2003284757A (ja) | 2002-01-24 | 2003-10-07 | Seputo:Kk | ヒーター付赤色光線治療器 |
AUPS146502A0 (en) | 2002-03-28 | 2002-05-09 | Traynor, Neil | Methods and apparatus relating to improved visual recognition and safety |
US6890719B2 (en) | 2002-05-10 | 2005-05-10 | The Board Of Trustess Of The University Of Illinois | Fluorescence based biosensor |
US7534560B2 (en) | 2002-05-10 | 2009-05-19 | The Board Of Trustees Of The University Of Illinois | Simple catalytic DNA biosensors for ions based on color changes |
JP4074136B2 (ja) | 2002-05-29 | 2008-04-09 | 浜松ホトニクス株式会社 | 蛍光寿命分布画像測定装置およびその測定方法 |
US7597876B2 (en) | 2007-01-11 | 2009-10-06 | Immunomedics, Inc. | Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules |
WO2004018478A2 (en) | 2002-08-23 | 2004-03-04 | Sloan-Kettering Institute For Cancer Research | Synthesis of epothilones, intermediates thereto, analogues and uses thereof |
US7005518B2 (en) | 2002-10-25 | 2006-02-28 | Li-Cor, Inc. | Phthalocyanine dyes |
US20040120949A1 (en) | 2002-11-08 | 2004-06-24 | Boehringer Ingelheim International Gmbh | Compositions and methods for treating cancer using cytotoxic CD44 antibody immunoconjugates and radiotherapy |
US20040202666A1 (en) | 2003-01-24 | 2004-10-14 | Immunomedics, Inc. | Anti-cancer anthracycline drug-antibody conjugates |
US7612185B2 (en) | 2003-03-07 | 2009-11-03 | The Board Of Trustees Of The University Of Illinois | Nucleic acid biosensors |
ATE442861T1 (de) | 2003-03-07 | 2009-10-15 | Univ Texas | Gegen antikörper gerichtete photodynamische therapie |
US20070020272A1 (en) | 2003-04-30 | 2007-01-25 | Tayyaba Hasan | Indirectly linked photosensitizer immunoconjugates, processes for the production thereof and methods of use thereof |
US7485419B2 (en) | 2004-01-13 | 2009-02-03 | The Board Of Trustees Of The University Of Illinois | Biosensors based on directed assembly of particles |
WO2006073419A2 (en) | 2004-04-01 | 2006-07-13 | Gang Zheng | Lipoprotein nanoplatforms |
US8211883B2 (en) | 2004-04-01 | 2012-07-03 | Case Western Reserve University | Topical delivery of phthalocyanines |
JP2008511856A (ja) | 2004-09-03 | 2008-04-17 | ハンツマン アドバンスト マテリアルズ (スイッツァランド) ゲーエムベーハー | フタロシアニン染料を含む組成物 |
US20060094026A1 (en) | 2004-11-03 | 2006-05-04 | Yi Lu | Nucleic acid enzyme light-up sensor utilizing invasive DNA |
EP1850874B1 (en) | 2005-02-23 | 2013-10-16 | Genentech, Inc. | Extending time to disease progression or survival in ovarian cancer patients using pertuzumab |
GB0504278D0 (en) | 2005-03-02 | 2005-04-06 | Khanzada Javed | Personal adornment |
US7892734B2 (en) | 2005-08-11 | 2011-02-22 | The Board Of Trustees Of The University Of Illinois | Aptamer based colorimetric sensor systems |
US8623354B2 (en) | 2005-09-07 | 2014-01-07 | Alchemia Oncology Pty Limited | Therapeutic compositions comprising hyaluronan and therapeutic antibodies as well as methods of treatment |
US20080095699A1 (en) | 2006-10-20 | 2008-04-24 | Shiying Zheng | Imaging contrast agents using nanoparticles |
DE102005059338A1 (de) | 2005-12-08 | 2007-06-14 | Carl Zeiss Jena Gmbh | Verfahren und Anordnung zur Untersuchung von Proben |
WO2007070680A2 (en) | 2005-12-16 | 2007-06-21 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Optically detectable probes for identification and treatment of tumors |
WO2008005942A2 (en) | 2006-06-30 | 2008-01-10 | The Govt. Of The Usa As Represented By The Secretary Of The Dept. Of Health And Human Services. | Activatable probes and methods of use |
US7993927B2 (en) | 2006-07-03 | 2011-08-09 | Beth Israel Deaconess Medical Center, Inc. | Histology methods |
JP2010522982A (ja) | 2007-03-29 | 2010-07-08 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | エラストマ層を含んでいる発光装置 |
US8058415B2 (en) | 2007-04-24 | 2011-11-15 | The Board Of Trustees Of The University Of Illinois | Aptamer- and nucleic acid enzyme-based systems for simultaneous detection of multiple analytes |
GB0711560D0 (en) | 2007-06-14 | 2007-07-25 | Innova Biosciences Ltd | Improvements in or relating to production of conjugates |
WO2009038776A1 (en) | 2007-09-18 | 2009-03-26 | Victor Manneh | Therapeutic nanoconjugates |
AU2008310664A1 (en) | 2007-10-12 | 2009-04-16 | Transmolecular, Inc. | Systemic administration of chlorotoxin agents for the diagnosis and treatment of tumors |
EP3320923B1 (en) | 2008-01-18 | 2022-04-06 | Visen Medical, Inc. | Fluorescent imaging agents |
US20110288234A1 (en) | 2008-02-19 | 2011-11-24 | The Research Foundation on State University of NY | Silica nanoparticles postloaded with photosensitizers for drug delivery in photodynamic therapy |
MX2010009530A (es) | 2008-02-27 | 2010-11-30 | Yeda Res & Dev | Conjugados de rgd-(bacterio) clorofila para terapia fotodinámica y formación de imágenes de tumores necróticos. |
NZ592241A (en) | 2008-09-15 | 2012-11-30 | Herlev Hospital | Ykl-40 as a marker for gastrointestinal cancers |
GB0819594D0 (en) | 2008-10-24 | 2008-12-03 | Univ Coimbrra | Process |
WO2010085651A1 (en) | 2009-01-23 | 2010-07-29 | The Penn State Research Foundation | In vivo photodynamic therapy of cancer via a near infrared agent encapsulated in calcium phosphate nanoparticles |
US8317737B2 (en) | 2009-02-25 | 2012-11-27 | The Invention Science Fund I, Llc | Device for actively removing a target component from blood or lymph of a vertebrate subject |
US8167871B2 (en) | 2009-02-25 | 2012-05-01 | The Invention Science Fund I, Llc | Device for actively removing a target cell from blood or lymph of a vertebrate subject |
GB0904825D0 (en) | 2009-03-20 | 2009-05-06 | Photobiotics Ltd | Biological materials and uses thereof |
WO2010121163A2 (en) | 2009-04-17 | 2010-10-21 | Li-Cor, Inc. | Fluorescent imaging with substituted cyanine dyes |
JP2013500991A (ja) | 2009-07-31 | 2013-01-10 | オーエスアイ・ファーマシューティカルズ,エルエルシー | mTOR阻害剤および血管新生阻害剤併用療法 |
US8401618B2 (en) | 2009-08-28 | 2013-03-19 | Visen Medical, Inc. | Systems and methods for tomographic imaging in diffuse media using a hybrid inversion technique |
WO2011038006A1 (en) | 2009-09-22 | 2011-03-31 | Visen Medical, Inc. | Systems and methods for virtual index-matching of diffusive media |
WO2011097248A2 (en) | 2010-02-02 | 2011-08-11 | Ventana Medical Systems, Inc. | Composition and method for stabilizing fluorescent particles |
WO2011123742A1 (en) | 2010-04-01 | 2011-10-06 | Baylor College Of Medicine | Non-radioactive agents for neuroblastoma imaging |
US8524239B2 (en) | 2010-07-09 | 2013-09-03 | The United States of America as represented by the Secrectary, Department of Health and Human Services | Photosensitizing antibody-fluorophore conjugates |
US20130287688A1 (en) | 2010-11-18 | 2013-10-31 | Xtuit Pharmaceuticals, Inc. | Novel compositions and uses of anti-hypertension agents for cancer therapy |
WO2012076631A1 (en) | 2010-12-07 | 2012-06-14 | Spectracure Ab | System and method for interstitial photodynamic light therapy in combination with photosensitizers |
US20140076404A1 (en) | 2010-12-15 | 2014-03-20 | Mei-Chee Tan | Ir-activated photoelectric systems |
WO2013044156A1 (en) | 2011-09-23 | 2013-03-28 | Li-Cor, Inc. | Application of reduced dyes in imaging |
JP6124143B2 (ja) | 2012-02-03 | 2017-05-10 | パナソニックIpマネジメント株式会社 | サラウンド成分生成装置 |
CN102585003B (zh) | 2012-02-06 | 2017-10-31 | 中国科学院福建物质结构研究所 | 肿瘤靶向光敏免疫偶联物的制备方法及其应用 |
EP2827906A1 (en) | 2012-03-21 | 2015-01-28 | Fraunhofer-Gesellschaft zur Förderung der Angewandten Forschung e.V. | Novel photoimmunoconjugates for use in photodynamic therapy |
US20160250337A9 (en) | 2012-04-17 | 2016-09-01 | Bahman Anvari | Biomedical imaging and therapy using red blood cells |
JP2016026471A (ja) | 2012-11-27 | 2016-02-18 | パナソニックヘルスケア株式会社 | 細胞識別分離方法および細胞識別分離装置 |
US20140220346A1 (en) | 2012-12-04 | 2014-08-07 | Memorial Sloan-Kettering Cancer Center | Modular polymer hydrogel nanoparticles and methods of their manufacture |
WO2014127365A1 (en) | 2013-02-15 | 2014-08-21 | Case Western Reserve University | Psma ligands and uses thereof |
EP2983677A4 (en) | 2013-04-08 | 2016-11-16 | Univ North Carolina | PHOTOSENSITIVE COMPOUNDS |
ES2729841T3 (es) | 2013-09-18 | 2019-11-06 | Aura Biosciences Inc | Conjugados de partículas similares a virus para tratar tumores |
US10232058B2 (en) | 2013-10-14 | 2019-03-19 | The Johns Hopkins University | Prostate-specific membrane antigen-targeted photosensitizers for photodynamic therapy |
EP3718570A1 (en) | 2014-06-02 | 2020-10-07 | Li-Cor, Inc. | Phthalocyanine probes and uses thereof |
SG11201610052TA (en) | 2014-08-08 | 2017-02-27 | Us Health | Photo-controlled removal of targets in vitro and in vivo |
EP3331909A1 (en) | 2015-08-07 | 2018-06-13 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Near infrared photoimmunotherapy (nir-pit) of suppressor cells to treat cancer |
NZ739780A (en) | 2015-08-18 | 2024-02-23 | Rakuten Medical Inc | Compositions, combinations and related methods for photoimmunotherapy |
EP3777978A1 (en) | 2015-08-18 | 2021-02-17 | Rakuten Medical, Inc. | Phthalocyanine dye conjugates and their storage |
US10416366B2 (en) | 2016-10-25 | 2019-09-17 | Rakuten Medical, Inc. | Light diffusing devices for use in photoimmunotherapy |
RU2741076C2 (ru) | 2016-10-25 | 2021-01-22 | Ракутен Медикал, Инк. | Светорассеивающие устройства для использования в фотоиммунотерапии |
AU2018225177A1 (en) | 2017-02-23 | 2019-09-05 | Rakuten Medical, Inc. | Therapeutic compositions and related methods for photoimmunotherapy |
BR112020000184B8 (pt) | 2017-07-07 | 2022-09-27 | Rakuten Medical Inc | Dispositivos de difusão de luz para uso em fotoimunoterapia |
JP2021521135A (ja) | 2018-04-10 | 2021-08-26 | ザ ユナイテッド ステイツ オブ アメリカ, アズ リプレゼンテッド バイ ザ セクレタリー, デパートメント オブ ヘルス アンド ヒューマン サービシーズ | がん細胞を標的とする近赤外光線免疫療法および宿主免疫活性化の組合せ |
-
2015
- 2015-08-07 SG SG11201610052TA patent/SG11201610052TA/en unknown
- 2015-08-07 CN CN201580034715.1A patent/CN106470705B/zh active Active
- 2015-08-07 EP EP15760320.0A patent/EP3177323B2/en active Active
- 2015-08-07 US US15/318,104 patent/US10830678B2/en active Active
- 2015-08-07 WO PCT/US2015/044168 patent/WO2016022896A1/en active Application Filing
- 2015-08-07 AU AU2015300915A patent/AU2015300915B2/en active Active
- 2015-08-07 JP JP2017506895A patent/JP6796058B2/ja active Active
- 2015-08-07 ES ES15760320T patent/ES2743458T5/es active Active
- 2015-08-07 CN CN202010317977.1A patent/CN111388672A/zh active Pending
- 2015-08-07 CA CA2954463A patent/CA2954463C/en active Active
-
2020
- 2020-04-06 JP JP2020068338A patent/JP7075435B2/ja active Active
- 2020-09-21 US US17/026,724 patent/US11781955B2/en active Active
- 2020-12-23 AU AU2020294224A patent/AU2020294224B2/en active Active
-
2022
- 2022-05-13 JP JP2022079474A patent/JP2022116064A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013009475A1 (en) * | 2011-07-11 | 2013-01-17 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Photosensitizing antibody-phuorophore conjugates |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11141483B2 (en) | 2015-08-18 | 2021-10-12 | Rakuten Medical, Inc. | Methods for manufacturing phthalocyanine dye conjugates and stable conjugates |
US11147875B2 (en) | 2015-08-18 | 2021-10-19 | Rakuten Medical, Inc. | Compositions, combinations and related methods for photoimmunotherapy |
US11154620B2 (en) | 2015-08-18 | 2021-10-26 | Rakuten Medical, Inc. | Compositions, combinations and related methods for photoimmunotherapy |
WO2019172110A1 (ja) * | 2018-03-09 | 2019-09-12 | 学校法人慈恵大学 | 血管を標的とする抗体と光増感剤とのコンジュゲート |
JPWO2019172110A1 (ja) * | 2018-03-09 | 2021-03-04 | 学校法人慈恵大学 | 血管を標的とする抗体と光増感剤とのコンジュゲート |
JP7216435B2 (ja) | 2018-03-09 | 2023-02-01 | 学校法人慈恵大学 | 血管を標的とする抗体と光増感剤とのコンジュゲート |
JP2021530558A (ja) * | 2018-06-21 | 2021-11-11 | 株式会社島津製作所 | 近赤外光免疫療法による治療法を試験するための方法 |
WO2020246350A1 (ja) * | 2019-06-03 | 2020-12-10 | 学校法人慈恵大学 | 殺菌剤 |
Also Published As
Publication number | Publication date |
---|---|
WO2016022896A1 (en) | 2016-02-11 |
CA2954463A1 (en) | 2016-02-11 |
US20210010914A1 (en) | 2021-01-14 |
CN111388672A (zh) | 2020-07-10 |
EP3177323B2 (en) | 2023-01-25 |
CN106470705A (zh) | 2017-03-01 |
AU2015300915A1 (en) | 2017-02-02 |
JP2022116064A (ja) | 2022-08-09 |
JP2020114864A (ja) | 2020-07-30 |
AU2020294224A1 (en) | 2021-01-28 |
EP3177323A1 (en) | 2017-06-14 |
JP6796058B2 (ja) | 2020-12-02 |
ES2743458T5 (es) | 2023-06-08 |
SG11201610052TA (en) | 2017-02-27 |
EP3177323B1 (en) | 2019-05-01 |
AU2020294224B2 (en) | 2022-10-27 |
CA2954463C (en) | 2023-11-07 |
US10830678B2 (en) | 2020-11-10 |
JP7075435B2 (ja) | 2022-05-25 |
US20170122853A1 (en) | 2017-05-04 |
ES2743458T3 (es) | 2020-02-19 |
US11781955B2 (en) | 2023-10-10 |
AU2015300915B2 (en) | 2020-09-24 |
CN106470705B (zh) | 2020-03-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7075435B2 (ja) | インビトロおよびインビボにおける標的の光制御除去 | |
JP7316862B2 (ja) | 小細胞肺癌に対する標的療法 | |
JP6970659B2 (ja) | がんを処置するためのサプレッサー細胞の近赤外光免疫療法(nir−pit) | |
US10196435B2 (en) | OX40L fusion protein for the immunotherapy of tumors of veterinary animals | |
HUE032623T2 (hu) | Anti-CXCR1 kompozíciók és módszerek | |
CN101506358A (zh) | 使用偶合的抗体或抗体片段治疗人免疫缺陷病毒感染的方法和组合物 | |
TW202102272A (zh) | 光免疫療法之方法及相關之生物標記 | |
JP2021521135A (ja) | がん細胞を標的とする近赤外光線免疫療法および宿主免疫活性化の組合せ | |
TW202110890A (zh) | 抗siglec-9組合物及其用於調節骨髓細胞發炎表型之方法及用途 | |
BR112021008263A2 (pt) | materiais e métodos para tratamento de câncer | |
JP2021525756A (ja) | 抗グロボh又は抗ssea−4抗体を、抗ネガティブ免疫チェックポイント抗体と共に使用することによる組合せ療法 | |
KR20210111770A (ko) | 조작된 플라겔린-유래 조성물 및 용도 | |
CN104826110A (zh) | 新一代多功能抗体纳米团簇的制备及其协同治疗应用 | |
JP2017500286A (ja) | 血液系腫瘍を治療するための方法 | |
JP2023549079A (ja) | 二重標的化キメラ抗原受容体 | |
JP2022513082A (ja) | 免疫応答を調節するためのIRE1α-XBP1シグナル伝達経路バイオマーカーの使用 | |
CN118119405A (zh) | B7-h3靶向融合蛋白及其使用方法 | |
KR20220152220A (ko) | Cd19-지시된 키메라 항원 수용체 t 세포 조성물 및 이의 방법 및 용도 | |
EP4277934A1 (en) | Her2 single domain antibodies variants and cars thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180619 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180619 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190425 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190724 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20191205 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200406 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20200406 |
|
C11 | Written invitation by the commissioner to file amendments |
Free format text: JAPANESE INTERMEDIATE CODE: C11 Effective date: 20200416 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20200518 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20200616 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20200617 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200709 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201006 |
|
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: 20201021 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20201113 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6796058 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |